G1 delay in cells overexpressing prostaglandin endoperoxide synthase-2

Raymond N. DuBois, Jinyi Shao, Masahiko Tsujii, Hongmiao Sheng, R. Daniel Beauchamp

    Research output: Contribution to journalArticlepeer-review

    188 Scopus citations


    Colorectal cancer is the second leading cause of death from cancer in the United States. Continuous use of aspirin and other nonsteroidal anti- inflammatory drugs (NSAIDs) has been shown to reduce the risk of colorectal cancer in humans by 40-50%. Patients with familial adenomatous polyposis who take NSAIDs, such as sulindac, undergo a regression of intestinal adenomas. Rodents exposed to carcinogens that cause colon cancer have a 50-60% reduction in the size and number of colonic tumors when treated continuously with NSAIDs. One common target for these drugs is prostaglandin endoperoxide synthase, also referred to as cyclooxygenase (COX). We and others have shown recently that COX-2 levels are increased dramatically in 85-90% of human colorectal adenocarcinomas and in 40-50% of colonic adenomas. We prepared intestinal epithelial cells that express the COX-2 gene permanently and found that they have altered adhesion properties and resist undergoing apoptosis. We report here that these cells also have a 3-fold increase in the duration of G1, lower levels of cyclin D1 protein, and a marked decrease in retinoblastoma kinase activity associated with cyclin-dependent kinase 4. The delay in G1 transit may relate to the resistance of these cells to undergo programmed cell death, which could affect their tumorigenic potential.

    Original languageEnglish (US)
    Pages (from-to)733-737
    Number of pages5
    JournalCancer Research
    Issue number4
    StatePublished - Feb 15 1996

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research


    Dive into the research topics of 'G1 delay in cells overexpressing prostaglandin endoperoxide synthase-2'. Together they form a unique fingerprint.

    Cite this