Women in hereditary nonpolyposis colorectal cancer (HNPCC) families have up to a 71% lifetime risk for developing endometrial cancer (EC). This compares to the female lifetime risk for colorectal cancer (CRC) in HNPCC of 60%. The basis of HNPCC is an inherited mutation in a mismatch repair gene (MMR). Aspirin and COX2 inhibitors seem to have a chemoprotective effect on CRC in the general population and are the subject of prospective clinical studies in patients at high risk for CRC including HNPCC. There is no evidence that these agents have any protective effect against EC in the general population. This study investigated the effect of aspirin and a COX2 inhibitor (rofecoxib) on an HNPCC EC cell line model (Ishikawa) by assessing the effect on proliferation, apoptosis, the cell cycle, and MMR gene expression. Aspirin inhibits EC cell proliferation by inducing apoptosis and changes in the cell cycle. This effect is not mediated by changes in MMR gene (hMSH2) expression as assessed by quantitative reverse transcription-polymerase chain reaction. Rofecoxib inhibits EC cell proliferation; this did not appear to be mediated by induction of apoptosis, by alterations of the cell cycle, or by changes in MMR gene expression.

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proliferation the cell cox2 inhibitor apoptosis ec mmr gene hmsh2 expression quantitative reverse transcriptionpolymerase chain reaction line mismatch repair gene

N J, Wood N A, Quinton S, Burdall E, Sheridan S R, Duffy,.Exploring the potential chemopreventative effect of aspirin and rofecoxib on hereditary nonpolyposis colorectal cancer-like endometrial cancer cells in vitro through mechanisms involving apoptosis, the cell cycle, and mismatch repair gene expression.. 17 (2),447-54.

N J, Wood N A, Quinton S, Burdall E, Sheridan S R, Duffy,"Exploring the potential chemopreventative effect of aspirin and rofecoxib on hereditary nonpolyposis colorectal cancer-like endometrial cancer cells in vitro through mechanisms involving apoptosis, the cell cycle, and mismatch repair gene expression." 17

N J, Wood N A, Quinton S, Burdall E, Sheridan S R, Duffy,"Exploring the potential chemopreventative effect of aspirin and rofecoxib on hereditary nonpolyposis colorectal cancer-like endometrial cancer cells in vitro through mechanisms involving apoptosis, the cell cycle, and mismatch repair gene expression."