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.
A method for diagnosing prostate cancer by detection of EN2 in urine has 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.
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, and available worldwide in 2 years.
^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 (March 2011). "Engrailed-2 (EN2): a tumor specific urinary biomarker for the early diagnosis of prostate cancer". Clin. Cancer Res.17 (5): 1090–8. doi:10.1158/1078-0432.CCR-10-2410. PMID21364037. Lay summary – BBC News.
Logan C, Hanks MC, Noble-Topham S; et al. (1993). "Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions.". Dev. Genet.13 (5): 345–58. doi:10.1002/dvg.1020130505. PMID1363401.
Joyner AL, Herrup K, Auerbach BA; et al. (1991). "Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox.". Science251 (4998): 1239–43. doi:10.1126/science.1672471. PMID1672471.
Joliot A, Trembleau A, Raposo G; et al. (1997). "Association of Engrailed homeoproteins with vesicles presenting caveolae-like properties". Development124 (10): 1865–75. PMID9169834.
, (1998). "A full genome screen for autism with evidence for linkage to a region on chromosome 7q. International Molecular Genetic Study of Autism Consortium". Hum. Mol. Genet.7 (3): 571–8. doi:10.1093/hmg/7.3.571. PMID9546821.
Philippe A, Martinez M, Guilloud-Bataille M; et al. (1999). "Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study". Hum. Mol. Genet.8 (5): 805–12. doi:10.1093/hmg/8.5.805. PMID10196369.
Sarnat HB, Benjamin DR, Siebert JR; et al. (2002). "Agenesis of the mesencephalon and metencephalon with cerebellar hypoplasia: putative mutation in the EN2 gene--report of 2 cases in early infancy". Pediatr. Dev. Pathol.5 (1): 54–68. doi:10.1007/s10024-001-0103-5. PMID11815869.
Foucher I, Montesinos ML, Volovitch M; et al. (2003). "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". Development130 (9): 1867–76. doi:10.1242/dev.00414. PMID12642491.
Gharani N, Benayed R, Mancuso V; et al. (2004). "Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder". Mol. Psychiatry9 (5): 474–84. doi:10.1038/sj.mp.4001498. PMID15024396.
Hjerrild M, Stensballe A, Rasmussen TE; et al. (2004). "Identification of phosphorylation sites in protein kinase A substrates using artificial neural networks and mass spectrometry". J. Proteome Res.3 (3): 426–33. doi:10.1021/pr0341033. PMID15253423.