title: Notch1 induces cell cycle arrest and apoptosis in human cervical cancer cells: involvement of nuclear factor kappa B inhibition.
abstract: Notch signaling can serve as a tumor suppressor or tumor promoter in the same kind of cancer, such as human papillomavirus-positive cervical cancer cells. However, the exact mechanisms remain poorly characterized. Our studies demonstrated that constitutively overexpressed active Notch1 via stable transfection with exogenous intracellular domain of Notch1 (ICN) resulted in growth inhibition of the human cervical cancer cell line HeLa by inducing G(2)-M arrest and apoptosis. Moreover, the growth inhibition was correlated with inhibition of nuclear factor kappa B (NF-kappaB) p50 activation, accompanied by a decrease in the nuclear expression of NF-kappaB p50 and an increase in the cytosolic expression of IkappaBalpha. Consistent with these results, downregulation of cyclin D1 and Bcl-2, which are both the downstream genes of NF-kappaB, were observed in ICN-overexpressed cells. Overall, our results suggest that NF-kappaB inhibition may contribute partially to cell cycle arrest and apoptosis induced by Notch1 activation in human cervical cancer cells.
authors.affiliation: Institute of Virology, School of Medicine, Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.forename: L
authors.initials: L
authors.lastname: Duan
authors.forename: M
authors.initials: M
authors.lastname: Fan
authors.forename: J
authors.initials: J
authors.lastname: Yuan
authors.forename: X
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D041681:NIH 3T3 Cells; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D016328:NF-kappa B; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1