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Achaete-scute like (ASCL)2 is a basic helix–loop–helix transcription factor essential for the maintenance of proliferating trophoblasts during placental development. Using oligonucleotide microarrays we identified ascl2 as a gene significantly upregulated in colorectal adenocarcinomas (n=36 cancers, n=16 normals; 15-fold, P<0.0001). This finding was confirmed by quantitative reverse transcriptase (RT)–PCR on large intestinal cancers (n=29 cancers, n=16 normals; 10-fold, P<0.0001). In situ hybridization for ascl2 demonstrated expression at the base of small and large intestinal crypts (n=304), but in no other normal tissues excepting placenta. By in situ hybridization, 52–71% of colorectal adenomas (n=187), 50–73% of large (n=327) and 33–64% of small intestinal adenocarcinomas (n=124) were positive for ascl2 expression. Upregulation of murine ascl2 was also observed using oligonucleotide microarrays, quantitative RT–PCR and in situ hybridization on apcmin/+ and apc1638N/+ smad4−/+ tumours. Tumour cell lines stably transfected with LEF1DN or APC2, or transiently transfected with short-interfering RNA (siRNA) against β-catenin showed a significant downregulation of ascl2. Colocalization of ascl2 with nuclear β-catenin was observed in 73 small intestinal adenocarcinomas (P=0.0008) and apcmin/+ tumours. Preliminary in vitro data suggest ascl2 may promote progression through the G2/M cell cycle checkpoint. In summary, ascl2 is a putative regulator of proliferation that is overexpressed in intestinal neoplasia.Oncogene (2006) 25, 3445–3457. doi:10.1038/sj.onc.1209382; published online 27 March 2006 [ABSTRACT FROM AUTHOR]

The neuregulins are a diverse family of proteins that play an important role in controlling the growth and differentiation of glial, epithelial and muscle cells. This review describes recent findings of novel neuregulins (NRG2 and NRG3) and summarizes the tissue distribution and receptor interaction of these ligands. [ABSTRACT FROM AUTHOR]