Appropriate cell cycle checkpoint is essential for the maintenance of normal cells and chemosensitivity of cancer cells . Clear cell adenocarcinoma (CCA) of the ovary is known to be highly resistant to chemotherapy. Hepatocyte Nuclear Factor-1 beta (HNF-1 beta) is known to be overexpressed in CCA, but its role and clinical significance has not been unclear. We investigated the role of HNF-1 beta in regulation of cell cycle in CCA.
To clarify the effects of HNF-1beta on cell cycle checkpoint, we compared the expression of key proteins involved in cell cycle checkpoints between TU-OC1 (CCA cell) cells stably knocking down of HNF1-beta and vector-control cell lines after exposure of bleomycin.
Cell cycle arrests induced by DNA damage were retained with sustained activation of ATM-Chk1 pathway and suppression of cell death in HNF-1beta overexpressing cells.
The chemoresistance of CCA may be due to aberrant retention of G2 checkpoint through overexpression of HNF-1 beta. Anticancer agents combined with Chk1 inhibitors may sensitize in CCA.
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