p21WAF1/cip1 is an important determinant of intestinal cell response to sulindac in vitro and in vivo Academic Article uri icon

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, p21(WAF1/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/.

authors

  • Yang, WC
  • Velcich, A
  • Mariadason, J
  • Nicholas, C
  • Corner, G
  • Houston, M
  • Augenlicht, LH
  • Edelmann, W
  • Augenlicht, LH
  • Kucherlapati, R
  • Holt, PR

publication date

  • August 15, 2001

has subject area