Biology:EN2 (gene)
 Generic protein structure example |
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
Homeobox-containing genes are thought to have a role in controlling development. In Drosophila, the 'engrailed' (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system.[1]
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]
Negative results
However, an independent study published in 2020 questioned the value of EN2 as a urinary marker for prostate cancer.[5] In a comparison between 90 PC patients and 30 healthy subjects, their results show that EN2 as a PC biomarker brings no additional value to the current use of PSA in clinical practice. Despite their announcement of new clinical trial in 2018,[6] the developers of the urinary EN2 test at the University of Surrey never registered such a trial at ClinicalTrials.gov or published any results of it.[7] Also, Randox Ltd, the diagnostic company which was to commercialize the urinary EN2, does not offer it any more in their product portfolio.
References
- ↑ 1.0 1.1 "Entrez Gene: EN2 engrailed homeobox 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2020.
- ↑ "Engrailed-2 (EN2): a tumor specific urinary biomarker for the early diagnosis of prostate cancer". Clinical Cancer Research 17 (5): 1090–8. March 2011. doi:10.1158/1078-0432.CCR-10-2410. PMID 21364037.
- Adam Brimelow (1 March 2011). "Prostate cancer test is 'twice as good', say researchers". BBC News. https://www.bbc.co.uk/news/health-12610972.
- ↑ "University of Surrey licenses the patented use of EN2 protein as a diagnostic biomarker for prostate and bladder cancer to ZEUS Scientific". 13 March 2013. 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/.
- ↑ "Licence deal brings breakthrough prostate cancer test closer to clinical use". 13 March 2013. http://www.surrey.ac.uk/mediacentre/press/2013/99537_licence_deal_brings_breakthrough_prostate_cancer_test_closer_to_clinical_use.htm.
- ↑ "Is Engrailed-2 (EN2) a truly promising biomarker in prostate cancer detection?". Biomarkers 25 (1): 34–39. February 2020. doi:10.1080/1354750X.2019.1690047. PMID 31692391.
- ↑ "Biomarkers – Engrailed-2 (EN2) Urine Test for the Diagnosis of Prostate Cancer". https://prostate-project.net/biomarkers-engrailed-2-en2-urine-test-for-the-diagnosis-of-prostate-cancer/.
- ↑ "Clinical Trials". https://www.clinicaltrials.gov/ct2/results?cond=&term=EN2&cntry=&state=&city=&dist=.
Further reading
- "The Engrailed homeobox genes determine the different foliation patterns in the vermis and hemispheres of the mammalian cerebellum". Development 137 (3): 519–29. February 2010. doi:10.1242/dev.027045. PMID 20081196.
- "Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions". Developmental Genetics 13 (5): 345–58. 1993. doi:10.1002/dvg.1020130505. PMID 1363401.
- "Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox". Science 251 (4998): 1239–43. March 1991. doi:10.1126/science.1672471. PMID 1672471. Bibcode: 1991Sci...251.1239J.
- "Isolation and chromosomal localization of the human En-2 gene". Genomics 4 (3): 225–31. April 1989. doi:10.1016/0888-7543(89)90324-8. PMID 2565873.
- "Chromosomal localization of the human homeo box-containing genes, EN1 and EN2". Genomics 4 (2): 206–9. February 1989. doi:10.1016/0888-7543(89)90301-7. PMID 2567700.
- "Deregulated expression of PAX5 in medulloblastoma". Proceedings of the National Academy of Sciences of the United States of America 92 (12): 5709–13. June 1995. doi:10.1073/pnas.92.12.5709. PMID 7777574. Bibcode: 1995PNAS...92.5709K.
- "Association of Engrailed homeoproteins with vesicles presenting caveolae-like properties". Development 124 (10): 1865–75. May 1997. doi:10.1242/dev.124.10.1865. PMID 9169834.
- "A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium". Human Molecular Genetics 7 (3): 571–8. March 1998. doi:10.1093/hmg/7.3.571. PMID 9546821.
- Sanger Centre, The; Washington University Genome Sequencing Cente, The (November 1998). "Toward a complete human genome sequence". Genome Research 8 (11): 1097–108. doi:10.1101/gr.8.11.1097. PMID 9847074.
- "Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study". Human Molecular Genetics 8 (5): 805–12. May 1999. doi:10.1093/hmg/8.5.805. PMID 10196369.
- "A genomic screen of autism: evidence for a multilocus etiology". American Journal of Human Genetics 65 (2): 493–507. August 1999. doi:10.1086/302497. PMID 10417292.
- "Genetic studies of autistic disorder and chromosome 7". Genomics 61 (3): 227–36. November 1999. doi:10.1006/geno.1999.5968. PMID 10552924.
- "An autosomal genomic screen for autism. Collaborative linkage study of autism". American Journal of Medical Genetics 88 (6): 609–15. December 1999. doi:10.1002/(SICI)1096-8628(19991215)88:6<609::AID-AJMG7>3.3.CO;2-C. PMID 10581478.
- "Agenesis of the mesencephalon and metencephalon with cerebellar hypoplasia: putative mutation in the EN2 gene--report of 2 cases in early infancy". Pediatric and Developmental Pathology 5 (1): 54–68. 2002. doi:10.1007/s10024-001-0103-5. PMID 11815869.
- "No association between the EN2 gene and autistic disorder". Journal of Medical Genetics 40 (1): 4e–4. January 2003. doi:10.1136/jmg.40.1.e4. PMID 12525552.
- "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". Development 130 (9): 1867–76. May 2003. doi:10.1242/dev.00414. PMID 12642491.
- "Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder". Molecular Psychiatry 9 (5): 474–84. May 2004. doi:10.1038/sj.mp.4001498. PMID 15024396.
- "Identification of phosphorylation sites in protein kinase A substrates using artificial neural networks and mass spectrometry". Journal of Proteome Research 3 (3): 426–33. 2004. doi:10.1021/pr0341033. PMID 15253423.
External links
- EN2+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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