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 | W Yang, A Velcich, J Mariadason, C Nicholas, G Corner, M Houston, W Edelmann, R Kucherlapati, P R Holt, L H Augenlicht |
Journal | Cancer research
(Cancer Res)
Vol. 61
Issue 16
Pg. 6297-302
(Aug 15 2001)
ISSN: 0008-5472 [Print] United States |
PMID | 11507085
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- CDKN1A protein, human
- Cdkn1a protein, mouse
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
- Sulindac
|
Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Colonic Neoplasms
(drug therapy, genetics, pathology)
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
(biosynthesis, genetics, physiology)
- Duodenum
(cytology, drug effects, physiology)
- Female
- Gene Dosage
- Gene Expression Regulation, Neoplastic
(drug effects)
- Gene Silencing
(drug effects, physiology)
- Genes, APC
- Humans
- Intestinal Mucosa
(cytology, drug effects, physiology)
- Male
- Mice
- Oligonucleotide Array Sequence Analysis
- Precancerous Conditions
(drug therapy, genetics, pathology)
- Rectum
(cytology, drug effects, physiology)
- Sulindac
(pharmacology)
|