“EN2 (gene)”的意思、由来-开放百科全书

Homeobox protein engrailed-2 is a protein that in humans is encoded by the EN2 gene.^[1] It is a member of the engrailed gene family.

Function

Description

The Engrailed-2 gene encodes for the Engrailed-2 homeobox transcription factor. The signaling molecule, fibroblast growth factor 8 (FGF8), controls the expression of the En2 gene. The isthmus organizer expresses varying concentrations of FGF8 that influence the En2 transcription factor. En2 transcription factor is involved in patterning the midbrain of the central nervous system during embryonic development. Specifically, it is required for proper positioning of folia in the developing hemispheres. It continues to regulate foliation throughout nervous system development. En2 patterns cerebellum foliation in the mediolateral axis. Several birth defects can arise from inadequate or abnormal En2 expression. Scientists use a mice model to study the effects of En2 knockout alleles on development. When the En2 gene is knocked out, vermis foliation patterning becomes extremely altered. Along with decreased cerebellum foliation complexity, mutations in the En2 gene result in a depleted vermis or an overly simplified foliation pattern. The Engrailed genes are essential to proper neural circuit development.

In cancer diagnosis

A method for diagnosing prostate cancer by detection of EN2 in urine has been developed. The results of a clinical trial of 288 men suggest that EN2 could be a marker for prostate cancer which might prove more reliable than current methods that use prostate-specific antigen (PSA). If effective, a urine test is considered easier and less embarrassing for the patient than blood tests or rectal examinations and, therefore, less likely to discourage early diagnosis. At the time of the report, it was not clear whether or not the EN2 test could distinguish between aggressive tumours that would require intervention and relatively benign ones that would not.^[2]

Licensing and marketing

The EN2 test for prostate cancer has been licensed to Zeus Scientific, as they reported in March 2013. In that announcement they said they expected the test to be submitted to the US-FDA in a year,^[3] and available worldwide in 2 years.^[4]

References

1. ^¹{{cite web | title = Entrez Gene: EN2 engrailed homeobox 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2020| access-date = }}
2. ^{{cite journal | vauthors = Morgan R, Boxall A, Bhatt A, Bailey M, Hindley R, Langley S, Whitaker HC, Neal DE, Ismail M, Whitaker H, Annels N, Michael A, Pandha H | title = Engrailed-2 (EN2): a tumor specific urinary biomarker for the early diagnosis of prostate cancer | journal = Clinical Cancer Research | volume = 17 | issue = 5 | pages = 1090–8 | date = March 2011 | pmid = 21364037 | doi = 10.1158/1078-0432.CCR-10-2410 | laysummary = https://www.bbc.co.uk/news/health-12610972 | laysource = BBC News }}
3. ^{{cite web |url=http://www.zeusscientific.com/news-events/news/single/n-action/detail/Item/article/university-of-surrey-licenses-the-patented-use-of-en2-protein-as-a-diagnostic-biomarker-for-prostate-1/ |title=University of Surrey licenses the patented use of EN2 protein as a diagnostic biomarker for prostate and bladder cancer to ZEUS Scientific |date=13 March 2013 }}
4. ^{{cite web |url=http://www.surrey.ac.uk/mediacentre/press/2013/99537_licence_deal_brings_breakthrough_prostate_cancer_test_closer_to_clinical_use.htm |title=Licence deal brings breakthrough prostate cancer test closer to clinical use |date = 13 March 2013 }}

Further reading

{{cite journal | vauthors = Cheng Y, Sudarov A, Szulc KU, Sgaier SK, Stephen D, Turnbull DH, Joyner AL | title = The Engrailed homeobox genes determine the different foliation patterns in the vermis and hemispheres of the mammalian cerebellum | journal = Development | volume = 137 | issue = 3 | pages = 519–29 | date = February 2010 | pmid = 20081196 | pmc = 2858911 | doi = 10.1242/dev.027045 }}

{{cite journal | vauthors = Logan C, Hanks MC, Noble-Topham S, Nallainathan D, Provart NJ, Joyner AL | title = Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions | journal = Developmental Genetics | volume = 13 | issue = 5 | pages = 345–58 | year = 1993 | pmid = 1363401 | doi = 10.1002/dvg.1020130505 }}

{{cite journal | vauthors = Joyner AL, Herrup K, Auerbach BA, Davis CA, Rossant J | title = Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox | journal = Science | volume = 251 | issue = 4998 | pages = 1239–43 | date = March 1991 | pmid = 1672471 | doi = 10.1126/science.1672471 }}

{{cite journal | vauthors = Poole SJ, Law ML, Kao FT, Lau YF | title = Isolation and chromosomal localization of the human En-2 gene | journal = Genomics | volume = 4 | issue = 3 | pages = 225–31 | date = April 1989 | pmid = 2565873 | doi = 10.1016/0888-7543(89)90324-8 }}

{{cite journal | vauthors = Logan C, Willard HF, Rommens JM, Joyner AL | title = Chromosomal localization of the human homeo box-containing genes, EN1 and EN2 | journal = Genomics | volume = 4 | issue = 2 | pages = 206–9 | date = February 1989 | pmid = 2567700 | doi = 10.1016/0888-7543(89)90301-7 }}

{{cite journal | vauthors = Kozmik Z, Sure U, Rüedi D, Busslinger M, Aguzzi A | title = Deregulated expression of PAX5 in medulloblastoma | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 12 | pages = 5709–13 | date = June 1995 | pmid = 7777574 | pmc = 41766 | doi = 10.1073/pnas.92.12.5709 }}

{{cite journal | vauthors = Joliot A, Trembleau A, Raposo G, Calvet S, Volovitch M, Prochiantz A | title = Association of Engrailed homeoproteins with vesicles presenting caveolae-like properties | journal = Development | volume = 124 | issue = 10 | pages = 1865–75 | date = May 1997 | pmid = 9169834 | doi = }}

{{cite journal | vauthors = | title = A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium | journal = Human Molecular Genetics | volume = 7 | issue = 3 | pages = 571–8 | date = March 1998 | pmid = 9546821 | doi = 10.1093/hmg/7.3.571 }}

{{cite journal | vauthors = | title = Toward a complete human genome sequence | journal = Genome Research | volume = 8 | issue = 11 | pages = 1097–108 | date = November 1998 | pmid = 9847074 | doi = 10.1101/gr.8.11.1097 }}

{{cite journal | vauthors = Philippe A, Martinez M, Guilloud-Bataille M, Gillberg C, Råstam M, Sponheim E, Coleman M, Zappella M, Aschauer H, Van Maldergem L, Penet C, Feingold J, Brice A, Leboyer M, van Malldergerme L | title = Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study | journal = Human Molecular Genetics | volume = 8 | issue = 5 | pages = 805–12 | date = May 1999 | pmid = 10196369 | doi = 10.1093/hmg/8.5.805 }}

{{cite journal | vauthors = Risch N, Spiker D, Lotspeich L, Nouri N, Hinds D, Hallmayer J, Kalaydjieva L, McCague P, Dimiceli S, Pitts T, Nguyen L, Yang J, Harper C, Thorpe D, Vermeer S, Young H, Hebert J, Lin A, Ferguson J, Chiotti C, Wiese-Slater S, Rogers T, Salmon B, Nicholas P, Petersen PB, Pingree C, McMahon W, Wong DL, Cavalli-Sforza LL, Kraemer HC, Myers RM | title = A genomic screen of autism: evidence for a multilocus etiology | journal = American Journal of Human Genetics | volume = 65 | issue = 2 | pages = 493–507 | date = August 1999 | pmid = 10417292 | pmc = 1377948 | doi = 10.1086/302497 }}

{{cite journal | vauthors = Ashley-Koch A, Wolpert CM, Menold MM, Zaeem L, Basu S, Donnelly SL, Ravan SA, Powell CM, Qumsiyeh MB, Aylsworth AS, Vance JM, Gilbert JR, Wright HH, Abramson RK, DeLong GR, Cuccaro ML, Pericak-Vance MA | title = Genetic studies of autistic disorder and chromosome 7 | journal = Genomics | volume = 61 | issue = 3 | pages = 227–36 | date = November 1999 | pmid = 10552924 | doi = 10.1006/geno.1999.5968 }}

{{cite journal | vauthors = Barrett S, Beck JC, Bernier R, Bisson E, Braun TA, Casavant TL, Childress D, Folstein SE, Garcia M, Gardiner MB, Gilman S, Haines JL, Hopkins K, Landa R, Meyer NH, Mullane JA, Nishimura DY, Palmer P, Piven J, Purdy J, Santangelo SL, Searby C, Sheffield V, Singleton J, Slager S | title = An autosomal genomic screen for autism. Collaborative linkage study of autism | journal = American Journal of Medical Genetics | volume = 88 | issue = 6 | pages = 609–15 | date = December 1999 | pmid = 10581478 | doi = 10.1002/(SICI)1096-8628(19991215)88:6<609::AID-AJMG7>3.3.CO;2-C }}

{{cite journal | vauthors = Sarnat HB, Benjamin DR, Siebert JR, Kletter GB, Cheyette SR | title = Agenesis of the mesencephalon and metencephalon with cerebellar hypoplasia: putative mutation in the EN2 gene--report of 2 cases in early infancy | journal = Pediatric and Developmental Pathology | volume = 5 | issue = 1 | pages = 54–68 | year = 2002 | pmid = 11815869 | doi = 10.1007/s10024-001-0103-5 }}

{{cite journal | vauthors = Zhong H, Serajee FJ, Nabi R, Huq AH | title = No association between the EN2 gene and autistic disorder | journal = Journal of Medical Genetics | volume = 40 | issue = 1 | pages = e4 | date = January 2003 | pmid = 12525552 | pmc = 1735256 | doi = 10.1136/jmg.40.1.e4 }}

{{cite journal | vauthors = Foucher I, Montesinos ML, Volovitch M, Prochiantz A, Trembleau A | title = Joint regulation of the MAP1B promoter by HNF3beta/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors | journal = Development | volume = 130 | issue = 9 | pages = 1867–76 | date = May 2003 | pmid = 12642491 | doi = 10.1242/dev.00414 }}

{{cite journal | vauthors = Gharani N, Benayed R, Mancuso V, Brzustowicz LM, Millonig JH | title = Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder | journal = Molecular Psychiatry | volume = 9 | issue = 5 | pages = 474–84 | date = May 2004 | pmid = 15024396 | doi = 10.1038/sj.mp.4001498 }}