Genomic analysis of ovarian cancers demonstrated a regional chromosomal increase in expression and gene duplication. TGF-.beta. stimulation indicated a link between SnoN RNA and TGF-.beta.. In TIOSE, SnoN protein levels were reduced 15 min post TGF-.beta.-stimulation, likely by proteosome-mediated degradation. SnoN inhibition decreased cell growth between 20 and 50% concurrent with increased p21 levels. Stable expression of SnoN led to growth arrest through induction of senescence. Collectively, these results implicate SnoN levels in multiple roles during ovarian carcinogenesis: promoting cellular proliferation in ovarian cancer cells and as a positive mediator of cell cycle arrest and senescence in non-transformed ovarian epithelial cells.
GOVERNMENT SUPPORT STATEMENT
This invention was made with government support under Grant Nos. CA123219-01A2, CA083639, CA16672 and CA64602, awarded by the National Cancer Institute, RO1-CA123219-01A2, awarded by the National Institutes of Health, and DE-AC03-76SF00098, awarded by the Department of Energy. The Government has certain rights in the invention.