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词条 HER2/neu
释义

  1. Name

  2. Gene

  3. Function

      Signal transduction  

  4. Clinical significance

      Cancer    Mutations  

  5. As a drug target

  6. Diagnostics

      Cancer biopsy    Serum  

  7. Interactions

  8. See also

  9. References

  10. Further reading

  11. External links

{{Infobox_gene}}Receptor tyrosine-protein kinase erbB-2, also known as CD340 (cluster of differentiation 340), proto-oncogene Neu, Erbb2 (rodent), or ERBB2 (human), is a protein that in humans is encoded by the ERBB2 gene. ERBB is abbreviated from erythroblastic oncogene B, a gene isolated from avian genome. It is also frequently called HER2 (from human epidermal growth factor receptor 2) or HER2/neu.[1][2][3]

HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. In recent years the protein has become an important biomarker and target of therapy for approximately 30% of breast cancer patients.[4]

Name

HER2 is so named because it has a similar structure to human epidermal growth factor receptor, or HER1. Neu is so named because it was derived from a rodent glioblastoma cell line, a type of neural tumor. ErbB-2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR. Molecular cloning of the gene showed that HER2, Neu, and ErbB-2 are all encoded by the same orthologs.[4]

Gene

ERBB2, a known proto-oncogene, is located at the long arm of human chromosome 17 (17q12).

Function

The ErbB family consists of four plasma membrane-bound receptor tyrosine kinases. One of which is erbB-2, and the other members being epidermal growth factor receptor, erbB-3 (neuregulin-binding; lacks kinase domain), and erbB-4. All four contain an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain that can interact with a multitude of signaling molecules and exhibit both ligand-dependent and ligand-independent activity. Notably, no ligands for HER2 have yet been identified.[5][6] HER2 can heterodimerise with any of the other three receptors and is considered to be the preferred dimerisation partner of the other ErbB receptors.[7]

Dimerisation results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways.

Signal transduction

Signaling pathways activated by HER2 include:[8]

  • mitogen-activated protein kinase (MAPK)
  • phosphoinositide 3-kinase (PI3K/Akt)
  • phospholipase C γ
  • protein kinase C (PKC)
  • Signal transducer and activator of transcription (STAT)

In summary, signaling through the ErbB family of receptors promotes cell proliferation and opposes apoptosis, and therefore must be tightly regulated to prevent uncontrolled cell growth from occurring.

Clinical significance

Cancer

Amplification, also known as the over-expression of the ERBB2 gene, occurs in approximately 15-30% of breast cancers.[9][10] It is strongly associated with increased disease recurrence and a poor prognosis.[11] Over-expression is also known to occur in ovarian,[12] stomach, adenocarcinoma of the lung[13] and aggressive forms of uterine cancer, such as uterine serous endometrial carcinoma,[14][15] e.g. HER-2 is over-expressed in approximately 7-34% of patients with gastric cancer[16][17] and in 30% of salivary duct carcinomas.[18]

HER2 is colocalised and most of the time, coamplified with the gene GRB7, which is a proto-oncogene associated with breast, testicular germ cell, gastric, and esophageal tumours.

HER2 proteins have been shown to form clusters in cell membranes that may play a role in tumorigenesis.[19][20]

Recent evidence has implicated HER2 signaling in resistance to the EGFR-targeted cancer drug cetuximab.[21]

Mutations

Furthermore, diverse structural alterations have been identified that cause ligand-independent firing of this receptor, doing so in the absence of receptor over-expression. HER2 is found in a variety of tumours and some of these tumours carry point mutations in the sequence specifying the transmembrane domain of HER2. Substitution of a valine for a glutamic acid in the transmembrane domain can result in the constitutive dimerisation of this protein in the absence of a ligand.[22]

HER2 mutations have been found in non-small-cell lung cancers (NSCLC) and can direct treatment.[23]

As a drug target

HER2 is the target of the monoclonal antibody trastuzumab (marketed as Herceptin). Trastuzumab is effective only in cancers where HER2 is over-expressed. One year of trastuzumab therapy is recommended for all patients with HER2-positive breast cancer who are also receiving chemotherapy.[24] Twelve months of trastuzumab therapy is optimal. Randomized trials have demonstrated no additional benefit beyond 12 months, whereas 6 months has been shown to be inferior to 12. Trastuzumab is administered intravenously weekly or every 3 weeks.[25]

An important downstream effect of trastuzumab binding to HER2 is an increase in p27, a protein that halts cell proliferation.[26] Another monoclonal antibody, Pertuzumab, which inhibits dimerisation of HER2 and HER3 receptors, was approved by the FDA for use in combination with trastuzumab in June 2012.

As of November 2015, there are a number of ongoing and recently completed clinical trials of novel targeted agents for HER2+ metastatic breast cancer, e.g. margetuximab.[27]

Additionally, NeuVax (Galena Biopharma) is a peptide-based immunotherapy that directs "killer" T cells to target and destroy cancer cells that express HER2. It has entered phase 3 clinical trials.

It has been found that patients with ER+ (Estrogen receptor positive)/HER2+ compared with ER-/HER2+ breast cancers may actually benefit more from drugs that inhibit the PI3K/AKT molecular pathway.[28]

Over-expression of HER2 can also be suppressed by the amplification of other genes. Research is currently being conducted to discover which genes may have this desired effect.

The expression of HER2 is regulated by signaling through estrogen receptors. Normally, estradiol and tamoxifen acting through the estrogen receptor down-regulate the expression of HER2. However, when the ratio of the coactivator AIB-3 exceeds that of the corepressor PAX2, the expression of HER2 is upregulated in the presence of tamoxifen, leading to tamoxifen-resistant breast cancer.[29][30]

{{Clear}}

Diagnostics

Cancer biopsy

HER2 testing is performed in breast cancer patients to assess prognosis and to determine suitability for trastuzumab therapy. It is important that trastuzumab is restricted to HER2-positive individuals as it is expensive and has been associated with cardiac toxicity.[31] For HER2-negative tumours, the risks of trastuzumab clearly outweigh the benefits.

Tests are usually performed on biopsy samples obtained by either fine-needle aspiration, core needle biopsy, vacuum-assisted breast biopsy, or surgical excision. Immunohistochemistry is used to measure the amount of HER2 protein present in the sample. Examples of this assay include HercepTest, Dako, Glostrup, and Denmark. The sample is given a score based on the cell membrane staining pattern. Specimens with equivocal IHC results should then be validated using fluorescence in situ hybridisation (FISH). FISH can be used to measure the number of copies of the gene which are present and is thought to be more reliable than IHC.[32]

Serum

The extracellular domain of HER2 can be shed from the surface of tumour cells and enter the circulation. Measurement of serum HER2 by enzyme-linked immunosorbent assay (ELISA) offers a far less invasive method of determining HER2 status than a biopsy and consequently has been extensively investigated. Results so far have suggested that changes in serum HER2 concentrations may be useful in predicting response to trastuzumab therapy.[33] However, its ability to determine eligibility for trastuzumab therapy is less clear.[34]

Interactions

HER2/neu has been shown to interact with:

{{div col|colwidth=20em}}
  • CTNNB1,[35][36][37]
  • DLG4,[38]
  • Erbin,[39][40][41]
  • GRB2,[42][43][44]
  • HSP90AA1,[45][46]
  • IL6ST,[47]
  • MUC1,[48][49]
  • PICK1[39] and
  • PIK3R2,[50]
  • PLCG1,[51][52] and
  • SHC1.[42][44][53]
{{Div col end}}

See also

  • Ann Marie Rogers, campaigned for UK NHS to provide Herceptin
  • SkBr3 Cell Line, over-expresses HER2

References

1. ^{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/2064|title=ERBB2 erb-b2 receptor tyrosine kinase 2 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-06-14}}
2. ^{{Cite web|url=https://ghr.nlm.nih.gov/gene/ERBB2|title=ERBB2|last=Reference|first=Genetics Home|website=Genetics Home Reference|access-date=2016-06-19}}
3. ^{{Cite book|url=https://books.google.com/books?id=xZoXBgAAQBAJ|title=Noninvasive Molecular Markers in Gynecologic Cancers|last=Barh|first=Debmalya|last2=Gunduz|first2=Mehmet | name-list-format = vanc |date=2015-01-22|publisher=CRC Press|page=427|isbn=9781466569393 }}
4. ^{{cite journal | vauthors = Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U | title = Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene | journal = Science | volume = 230 | issue = 4730 | pages = 1132–9 | date = December 1985 | pmid = 2999974 | doi = 10.1126/science.2999974 | bibcode = 1985Sci...230.1132C }}
5. ^{{cite journal | vauthors = Keshamouni VG, Mattingly RR, Reddy KB | title = Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta | journal = The Journal of Biological Chemistry | volume = 277 | issue = 25 | pages = 22558–65 | date = June 2002 | pmid = 11960991 | doi = 10.1074/jbc.M202351200 }}
6. ^{{cite journal | vauthors = Rusnak DW, Affleck K, Cockerill SG, Stubberfield C, Harris R, Page M, Smith KJ, Guntrip SB, Carter MC, Shaw RJ, Jowett A, Stables J, Topley P, Wood ER, Brignola PS, Kadwell SH, Reep BR, Mullin RJ, Alligood KJ, Keith BR, Crosby RM, Murray DM, Knight WB, Gilmer TM, Lackey K | display-authors = 6 | title = The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: potential therapy for cancer | journal = Cancer Research | volume = 61 | issue = 19 | pages = 7196–203 | date = October 2001 | pmid = 11585755 }}
7. ^{{cite journal | vauthors = Olayioye MA | title = Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members | journal = Breast Cancer Research | volume = 3 | issue = 6 | pages = 385–9 | year = 2001 | pmid = 11737890 | pmc = 138705 | doi = 10.1186/bcr327 }}
8. ^{{cite journal | vauthors = Roy V, Perez EA | title = Beyond trastuzumab: small molecule tyrosine kinase inhibitors in HER-2-positive breast cancer | journal = The Oncologist | volume = 14 | issue = 11 | pages = 1061–9 | date = November 2009 | pmid = 19887469 | doi = 10.1634/theoncologist.2009-0142 }}
9. ^1 {{cite journal | vauthors = Mitri Z, Constantine T, O'Regan R | title = The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in Therapy | journal = Chemotherapy Research and Practice | volume = 2012 | issue = | pages = 743193 | year = 2012 | pmid = 23320171 | pmc = 3539433 | doi = 10.1155/2012/743193 }}
10. ^{{cite journal | vauthors = Burstein HJ | title = The distinctive nature of HER2-positive breast cancers | journal = The New England Journal of Medicine | volume = 353 | issue = 16 | pages = 1652–4 | date = October 2005 | pmid = 16236735 | doi = 10.1056/NEJMp058197 }}
11. ^{{cite journal | vauthors = Tan M, Yu D | title = Molecular mechanisms of erbB2-mediated breast cancer chemoresistance | journal = Advances in Experimental Medicine and Biology | volume = 608 | issue = | pages = 119–29 | year = 2007 | pmid = 17993237 | doi = 10.1007/978-0-387-74039-3_9 | isbn = 978-0-387-74037-9 | series = Advances in Experimental Medicine and Biology }}
12. ^{{cite book |last1=Kumar |first=Vinay |last2=Abbas |first2=Abul |last3=Aster |first3=Jon | name-list-format = vanc | date=2013 |title=Robbins basic pathology |location=Philadelphia |publisher=Elsevier/Saunders |page=697 |isbn=9781437717815}}
13. ^{{cite book |last1=Kumar |first=Vinay |last2=Abbas |first2=Abul |last3=Aster |first3=Jon | name-list-format = vanc | date=2013 |title=Robbins basic pathology |location=Philadelphia |publisher=Elsevier/Saunders |page=179 |isbn=9781437717815}}
14. ^{{cite journal | vauthors = Santin AD, Bellone S, Roman JJ, McKenney JK, Pecorelli S | title = Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu | journal = International Journal of Gynaecology and Obstetrics | volume = 102 | issue = 2 | pages = 128–31 | date = August 2008 | pmid = 18555254 | doi = 10.1016/j.ijgo.2008.04.008 }}
15. ^{{cite journal | vauthors = Buza N, Roque DM, Santin AD | title = HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges | journal = Archives of Pathology & Laboratory Medicine | volume = 138 | issue = 3 | pages = 343–50 | date = March 2014 | pmid = 24576030 | doi = 10.5858/arpa.2012-0416-RA }}
16. ^{{cite journal | vauthors = Rüschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, van de Vijver M, Viale G | title = HER2 testing in gastric cancer: a practical approach | journal = Modern Pathology | volume = 25 | issue = 5 | pages = 637–50 | date = May 2012 | pmid = 22222640 | doi = 10.1038/modpathol.2011.198 }}
17. ^{{cite journal | vauthors = Meza-Junco J, Au HJ, Sawyer MB | title = Critical appraisal of trastuzumab in treatment of advanced stomach cancer | journal = Cancer Management and Research | volume = 3 | issue = 3 | pages = 57–64 | year = 2011 | pmid = 21556317 | pmc = 3085240 | doi = 10.2147/CMAR.S12698 }}
18. ^{{cite journal | vauthors = Chiosea SI, Williams L, Griffith CC, Thompson LD, Weinreb I, Bauman JE, Luvison A, Roy S, Seethala RR, Nikiforova MN | title = Molecular characterization of apocrine salivary duct carcinoma | journal = The American Journal of Surgical Pathology | volume = 39 | issue = 6 | pages = 744–52 | date = June 2015 | pmid = 25723113 | doi = 10.1097/PAS.0000000000000410 }}
19. ^{{cite journal | vauthors = Nagy P, Jenei A, Kirsch AK, Szöllosi J, Damjanovich S, Jovin TM | title = Activation-dependent clustering of the erbB2 receptor tyrosine kinase detected by scanning near-field optical microscopy | journal = Journal of Cell Science | volume = 112 | issue = 11 | pages = 1733–41 | date = June 1999 | pmid = 10318765 | doi = }}
20. ^{{cite journal | vauthors = Kaufmann R, Müller P, Hildenbrand G, Hausmann M, Cremer C | title = Analysis of Her2/neu membrane protein clusters in different types of breast cancer cells using localization microscopy | journal = Journal of Microscopy | volume = 242 | issue = 1 | pages = 46–54 | date = April 2011 | pmid = 21118230 | doi = 10.1111/j.1365-2818.2010.03436.x }}
21. ^{{cite journal | vauthors = Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, Ercan D, Rogers A, Roncalli M, Takeda M, Fujisaka Y, Philips J, Shimizu T, Maenishi O, Cho Y, Sun J, Destro A, Taira K, Takeda K, Okabe T, Swanson J, Itoh H, Takada M, Lifshits E, Okuno K, Engelman JA, Shivdasani RA, Nishio K, Fukuoka M, Varella-Garcia M, Nakagawa K, Jänne PA | display-authors = 6 | title = Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab | journal = Science Translational Medicine | volume = 3 | issue = 99 | pages = 99ra86 | date = September 2011 | pmid = 21900593 | pmc = 3268675 | doi = 10.1126/scitranslmed.3002442 }}
22. ^{{cite journal | vauthors = Brandt-Rauf PW, Rackovsky S, Pincus MR | title = Correlation of the structure of the transmembrane domain of the neu oncogene-encoded p185 protein with its function | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 21 | pages = 8660–4 | date = November 1990 | pmid = 1978329 | pmc = 55017 | doi = 10.1073/pnas.87.21.8660 | bibcode = 1990PNAS...87.8660B }}
23. ^{{cite journal | vauthors = Mazières J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, Besse B, Blons H, Mansuet-Lupo A, Urban T, Moro-Sibilot D, Dansin E, Chouaid C, Wislez M, Diebold J, Felip E, Rouquette I, Milia JD, Gautschi O | display-authors = 6 | title = Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives | journal = Journal of Clinical Oncology | volume = 31 | issue = 16 | pages = 1997–2003 | date = June 2013 | pmid = 23610105 | doi = 10.1200/JCO.2012.45.6095 }}
24. ^{{cite journal | vauthors = Mates M, Fletcher GG, Freedman OC, Eisen A, Gandhi S, Trudeau ME, Dent SF | title = Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline | journal = Current Oncology | volume = 22 | issue = Suppl 1 | pages = S114-22 | date = March 2015 | pmid = 25848335 | pmc = 4381787 | doi = 10.3747/co.22.2322 }}
25. ^{{Cite book|title=Harrison's Principles of Internal Medicine |edition=20th |last=Jameson|display-authors=etal|first=|publisher=McGraw-Hill Education|year=2018|isbn=978-1-259-64403-0|location=|pages=Chapter 75: Breast Cancer}}
26. ^{{cite journal | vauthors = Le XF, Pruefer F, Bast RC | title = HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways | journal = Cell Cycle | volume = 4 | issue = 1 | pages = 87–95 | date = January 2005 | pmid = 15611642 | doi = 10.4161/cc.4.1.1360 }}
27. ^{{cite journal | vauthors = Jiang H, Rugo HS | title = Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options | journal = Therapeutic Advances in Medical Oncology | volume = 7 | issue = 6 | pages = 321–39 | date = November 2015 | pmid = 26557900 | pmc = 4622301 | doi = 10.1177/1758834015599389 }}
28. ^{{cite journal | vauthors = Loi S, Sotiriou C, Haibe-Kains B, Lallemand F, Conus NM, Piccart MJ, Speed TP, McArthur GA | title = Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer | journal = BMC Medical Genomics | volume = 2 | issue = | pages = 37 | year = 2009 | pmid = 19552798 | pmc = 2706265 | doi = 10.1186/1755-8794-2-37 | laysummary = https://www.sciencedaily.com/releases/2010/05/100506112557.htm | laysource = ScienceDaily }}
29. ^{{cite web | url = http://cordis.europa.eu/fetch?CALLER=EN_NEWS&ACTION=D&SESSION=&RCN=30093 | title = Study sheds new light on tamoxifen resistance | authorlink = | date = 2008-11-13 | format = | work = Cordis News | publisher = Cordis | pages = | quote = | accessdate = 2008-11-14}}
30. ^{{cite journal | vauthors = Hurtado A, Holmes KA, Geistlinger TR, Hutcheson IR, Nicholson RI, Brown M, Jiang J, Howat WJ, Ali S, Carroll JS | title = Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen | journal = Nature | volume = 456 | issue = 7222 | pages = 663–6 | date = December 2008 | pmid = 19005469 | pmc = 2920208 | doi = 10.1038/nature07483 | bibcode = 2008Natur.456..663H }}
31. ^{{cite journal | vauthors = Telli ML, Hunt SA, Carlson RW, Guardino AE | title = Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility | journal = Journal of Clinical Oncology | volume = 25 | issue = 23 | pages = 3525–33 | date = August 2007 | pmid = 17687157 | doi = 10.1200/JCO.2007.11.0106 }}
32. ^{{cite book | vauthors = Giuliano AE, Hurvitz SA | chapter = Breast Disorder | veditors = Papadakis MA, McPhee SJ, Rabow MW | title = Current Medical Diagnosis & Treatment | year = 2019 | location = New York, NY | publisher = McGraw-Hill }}
33. ^{{cite journal | vauthors = Ali SM, Carney WP, Esteva FJ, Fornier M, Harris L, Köstler WJ, Lotz JP, Luftner D, Pichon MF, Lipton A | title = Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer | journal = Cancer | volume = 113 | issue = 6 | pages = 1294–301 | date = September 2008 | pmid = 18661530 | doi = 10.1002/cncr.23689 }}
34. ^{{cite journal | vauthors = Lennon S, Barton C, Banken L, Gianni L, Marty M, Baselga J, Leyland-Jones B | title = Utility of serum HER2 extracellular domain assessment in clinical decision making: pooled analysis of four trials of trastuzumab in metastatic breast cancer | journal = Journal of Clinical Oncology | volume = 27 | issue = 10 | pages = 1685–93 | date = April 2009 | pmid = 19255335 | doi = 10.1200/JCO.2008.16.8351 }}
35. ^{{cite journal | vauthors = Schroeder JA, Adriance MC, McConnell EJ, Thompson MC, Pockaj B, Gendler SJ | title = ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas | journal = The Journal of Biological Chemistry | volume = 277 | issue = 25 | pages = 22692–8 | date = June 2002 | pmid = 11950845 | doi = 10.1074/jbc.M201975200 }}
36. ^{{cite journal | vauthors = Bonvini P, An WG, Rosolen A, Nguyen P, Trepel J, Garcia de Herreros A, Dunach M, Neckers LM | title = Geldanamycin abrogates ErbB2 association with proteasome-resistant beta-catenin in melanoma cells, increases beta-catenin-E-cadherin association, and decreases beta-catenin-sensitive transcription | journal = Cancer Research | volume = 61 | issue = 4 | pages = 1671–7 | date = February 2001 | pmid = 11245482 | doi = }}
37. ^{{cite journal | vauthors = Kanai Y, Ochiai A, Shibata T, Oyama T, Ushijima S, Akimoto S, Hirohashi S | title = c-erbB-2 gene product directly associates with beta-catenin and plakoglobin | journal = Biochemical and Biophysical Research Communications | volume = 208 | issue = 3 | pages = 1067–72 | date = March 1995 | pmid = 7702605 | doi = 10.1006/bbrc.1995.1443 }}
38. ^{{cite journal | vauthors = Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS, Pelkey KA, Yang DJ, Xiong WC, Salter MW, Mei L | title = Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses | journal = Neuron | volume = 26 | issue = 2 | pages = 443–55 | date = May 2000 | pmid = 10839362 | doi = 10.1016/s0896-6273(00)81176-9 }}
39. ^1 {{cite journal | vauthors = Jaulin-Bastard F, Saito H, Le Bivic A, Ollendorff V, Marchetto S, Birnbaum D, Borg JP | title = The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins | journal = The Journal of Biological Chemistry | volume = 276 | issue = 18 | pages = 15256–63 | date = May 2001 | pmid = 11278603 | doi = 10.1074/jbc.M010032200 }}
40. ^{{cite journal | vauthors = Bilder D, Birnbaum D, Borg JP, Bryant P, Huigbretse J, Jansen E, Kennedy MB, Labouesse M, Legouis R, Mechler B, Perrimon N, Petit M, Sinha P | title = Collective nomenclature for LAP proteins | journal = Nature Cell Biology | volume = 2 | issue = 7 | pages = E114 | date = July 2000 | pmid = 10878817| doi = 10.1038/35017119 }}
41. ^{{cite journal | vauthors = Huang YZ, Zang M, Xiong WC, Luo Z, Mei L | title = Erbin suppresses the MAP kinase pathway | journal = The Journal of Biological Chemistry | volume = 278 | issue = 2 | pages = 1108–14 | date = January 2003 | pmid = 12379659 | doi = 10.1074/jbc.M205413200 }}
42. ^1 {{cite journal | vauthors = Schulze WX, Deng L, Mann M | title = Phosphotyrosine interactome of the ErbB-receptor kinase family | journal = Molecular Systems Biology | volume = 1 | issue = | pages = 2005.0008 | year = 2005 | pmid = 16729043 | pmc = 1681463 | doi = 10.1038/msb4100012 }}
43. ^{{cite journal | vauthors = Bourguignon LY, Zhu H, Zhou B, Diedrich F, Singleton PA, Hung MC | title = Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth | journal = The Journal of Biological Chemistry | volume = 276 | issue = 52 | pages = 48679–92 | date = December 2001 | pmid = 11606575 | doi = 10.1074/jbc.M106759200 }}
44. ^1 {{cite journal | vauthors = Olayioye MA, Graus-Porta D, Beerli RR, Rohrer J, Gay B, Hynes NE | title = ErbB-1 and ErbB-2 acquire distinct signaling properties dependent upon their dimerization partner | journal = Molecular and Cellular Biology | volume = 18 | issue = 9 | pages = 5042–51 | date = September 1998 | pmid = 9710588 | pmc = 109089 | doi = 10.1128/mcb.18.9.5042 }}
45. ^{{cite journal | vauthors = Xu W, Mimnaugh E, Rosser MF, Nicchitta C, Marcu M, Yarden Y, Neckers L | title = Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 5 | pages = 3702–8 | date = February 2001 | pmid = 11071886 | doi = 10.1074/jbc.M006864200 }}
46. ^{{cite journal | vauthors = Jeong JH, An JY, Kwon YT, Li LY, Lee YJ | title = Quercetin-induced ubiquitination and down-regulation of Her-2/neu | journal = Journal of Cellular Biochemistry | volume = 105 | issue = 2 | pages = 585–95 | date = October 2008 | pmid = 18655187 | pmc = 2575035 | doi = 10.1002/jcb.21859 }}
47. ^{{cite journal | vauthors = Grant SL, Hammacher A, Douglas AM, Goss GA, Mansfield RK, Heath JK, Begley CG | title = An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells | journal = Oncogene | volume = 21 | issue = 3 | pages = 460–74 | date = January 2002 | pmid = 11821958 | doi = 10.1038/sj.onc.1205100 }}
48. ^{{cite journal | vauthors = Li Y, Yu WH, Ren J, Chen W, Huang L, Kharbanda S, Loda M, Kufe D | title = Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein | journal = Molecular Cancer Research | volume = 1 | issue = 10 | pages = 765–75 | date = August 2003 | pmid = 12939402 | doi = }}
49. ^{{cite journal | vauthors = Schroeder JA, Thompson MC, Gardner MM, Gendler SJ | title = Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland | journal = The Journal of Biological Chemistry | volume = 276 | issue = 16 | pages = 13057–64 | date = April 2001 | pmid = 11278868 | doi = 10.1074/jbc.M011248200 }}
50. ^{{cite journal | vauthors = Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD | title = Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system | journal = The Biochemical Journal | volume = 288 | issue = 2 | pages = 395–405 | date = December 1992 | pmid = 1334406 | pmc = 1132024 | doi = 10.1042/bj2880395 }}
51. ^{{cite journal | vauthors = Peles E, Levy RB, Or E, Ullrich A, Yarden Y | title = Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma | journal = The EMBO Journal | volume = 10 | issue = 8 | pages = 2077–86 | date = August 1991 | pmid = 1676673 | pmc = 452891 | doi = }}
52. ^{{cite journal | vauthors = Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL | title = Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 23 | pages = 10435–9 | date = December 1991 | pmid = 1683701 | pmc = 52943 | doi = 10.1073/pnas.88.23.10435 | bibcode = 1991PNAS...8810435A }}
53. ^{{cite journal | vauthors = Wong L, Deb TB, Thompson SA, Wells A, Johnson GR | title = A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling | journal = The Journal of Biological Chemistry | volume = 274 | issue = 13 | pages = 8900–9 | date = March 1999 | pmid = 10085134 | doi = 10.1074/jbc.274.13.8900 }}

Further reading

{{refbegin|33em}}
  • {{cite journal | vauthors = Ross JS, Fletcher JA, Linette GP, Stec J, Clark E, Ayers M, Symmans WF, Pusztai L, Bloom KJ | title = The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy | journal = The Oncologist | volume = 8 | issue = 4 | pages = 307–25 | year = 2003 | pmid = 12897328 | doi = 10.1634/theoncologist.8-4-307 }}
  • {{cite journal | vauthors = Zhou BP, Hung MC | title = Dysregulation of cellular signaling by HER2/neu in breast cancer | journal = Seminars in Oncology | volume = 30 | issue = 5 Suppl 16 | pages = 38–48 | date = October 2003 | pmid = 14613025 | doi = 10.1053/j.seminoncol.2003.08.006 }}
  • {{cite journal | vauthors = Ménard S, Casalini P, Campiglio M, Pupa SM, Tagliabue E | title = Role of HER2/neu in tumor progression and therapy | journal = Cellular and Molecular Life Sciences | volume = 61 | issue = 23 | pages = 2965–78 | date = December 2004 | pmid = 15583858 | doi = 10.1007/s00018-004-4277-7 }}
  • {{cite journal | vauthors = Becker JC, Muller-Tidow C, Serve H, Domschke W, Pohle T | title = Role of receptor tyrosine kinases in gastric cancer: new targets for a selective therapy | journal = World Journal of Gastroenterology | volume = 12 | issue = 21 | pages = 3297–305 | date = June 2006 | pmid = 16733844 | pmc = 4087885 | doi = 10.3748/wjg.v12.i21.3297 }}
  • {{cite journal | vauthors = Laudadio J, Quigley DI, Tubbs R, Wolff DJ | title = HER2 testing: a review of detection methodologies and their clinical performance | journal = Expert Review of Molecular Diagnostics | volume = 7 | issue = 1 | pages = 53–64 | date = January 2007 | pmid = 17187484 | doi = 10.1586/14737159.7.1.53 }}
  • {{cite journal | vauthors = Bianchi F, Tagliabue E, Ménard S, Campiglio M | title = Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections | journal = Cell Cycle | volume = 6 | issue = 6 | pages = 643–6 | date = March 2007 | pmid = 17374991 | doi = 10.4161/cc.6.6.4033 }}
{{refend}}

External links

  • ERBB2 expression across human cancerous and healthy tissues{{dead link|date=October 2017 |bot=InternetArchiveBot |fix-attempted=yes }}
  • [https://web.archive.org/web/20080516045758/http://www.aacr.org/home/public--media/for-the-media/fact-sheets/cancer-concepts/her2.aspx AACR Cancer Concepts Factsheet on HER2]
  • [https://web.archive.org/web/20081011055216/http://www.her2.co.za/care/ Breast Friends for Life Network - A South African Breast Cancer Support Forum for HER2 Positive Women]
  • HerceptinR : Herceptin Resistance Database for Understanding Mechanism of Resistance in Breast Cancer Patients. Sci. Rep. 4:4483
  • {{MeshName|Receptor,+erbB-2}}
{{PDB Gallery|geneid=2064}}{{Clusters of differentiation}}{{Oncogenes}}{{Tumor markers}}{{Tyrosine kinases}}{{Enzymes}}{{Growth factor receptor modulators}}{{Portal bar|Molecular and Cellular Biology|border=no}}{{DEFAULTSORT:Her2 Neu}}

3 : Clusters of differentiation|Tyrosine kinase receptors|Cancer treatments
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