Lack of cyclooxygenase-2 activity in HT-29 human colorectal carcinoma cells

Induction of cyclooxygenase-2 (COX-2) is an early event in the sequence of polyp formation to colon carcinogenesis, COX-2 is at elevated levels in hum an colorectal cancers and in tumors and polyps of mouse models of colorecta l cancer, Mutation of the adenomatous polyposis coli (APC) gene is the init ial event leading to colorectal cancer, Colorectal cells in culture which e xpress mutant APC are often used to examine the association of COX-2 expres sion and apoptosis, The expression of full-length APC in HT-29 cells, a hum an colorectal carcinoma cell line which normally expresses truncated APC an d highly expresses COX-2, inhibits cell growth through increased apoptosis and results in a down-regulation of COX-2 protein, In this report, we exami ne whether down-regulation of COX-2 is directly linked to the increase in a poptosis observed in these HT-29-APC cells, We present evidence that COX-2 and apoptosis are not linked since COX-2, although expressed, is catalytica lly inactive. Interestingly, the COX-2 cloned from HT-29 cells is catalytic ally active when transfected into HCT-116 cells, a colorectal cell line whi ch normally does not express COX-2, but is not active in the HT-29 cell lin e itself.