Abstract
Sulindac, a nonsteroidal anti-inflammatory drug, inhibits intestinal tumorigenesis in humans and rodents. Sulindac induced complex alterations in gene expression, but only 0.1% of 8063 sequences assayed were altered similarly by the drug in rectal biopsies of patients treated for 1 month and during response of colonic cells in culture. Among these changes was induction of the cyclin-dependent kinase inhibitor, p21WAF1/cip1. In Apc1638+/ mice, targeted inactivation of p21 increased intestinal tumor formation in a gene-dose-dependent manner, but inactivation of p21 completely eliminated the ability of sulindac to both inhibit mitotic activity in the duodenal mucosa and to inhibit Apc-initiated tumor formation. Thus, p21 is essential for tumor inhibition by this drug. The array data can be accessed on the Internet at http://sequence.aecom.yu.edu/genome/.
Original language | English (US) |
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Pages (from-to) | 6297-6302 |
Number of pages | 6 |
Journal | Cancer research |
Volume | 61 |
Issue number | 16 |
State | Published - Aug 15 2001 |
ASJC Scopus subject areas
- Oncology
- Cancer Research