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

Wan Cai Yang, Anna Velcich, John Mariadason, Courtney Nicholas, Georgia Corner, Michele Houston, Leonard H. Augenlicht, Winfried Edelmann, Leonard H. Augenlicht, Raju Kucherlapati, Peter R. Holt

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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 languageEnglish (US)
Pages (from-to)6297-6302
Number of pages6
JournalCancer research
Volume61
Issue number16
StatePublished - Aug 15 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'p21<sup>WAF1/cip1</sup> is an important determinant of intestinal cell response to sulindac in vitro and in vivo'. Together they form a unique fingerprint.

Cite this