Signaling-mediated epigenetic silencing of tumor suppressor genes in ovarian cancer

Aberrant TGFβ signaling pathway may alter the expression of down-stream targets and promotes ovarian carcinogenesis. However, the mechanism of this impairment is not fully understood. By ChIP-chip and expression microarray, we have previously identified several SMAD4 targets in an immortalized ovarian surface epithelial cells. Bioinformatic analyses identified several SMAD transcriptional modules that predict expression changes after TGF-β activation. Knockdown of SMAD4 in CP70 ovarian cancer cells showed an increase in promoter methylation in some of those SMAD4 targets as demonstrated by sequencing-based analysis.