Clinical Cancer Research, Vol 1, Issue 11 1421-1428, Copyright © 1995 by American Association for Cancer Research

ARTICLES

Elevated levels of 2',5'-linked oligoadenylate-dependent ribonuclease L occur as an early event in colorectal tumorigenesis

L Wang, A Zhou, S Vasavada, B Dong, H Nie, JM Church, BR Williams, S Banerjee and RH Silverman
Departments of Cancer Biology, Urology, and Colorectal Surgery, Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

RNA decay in IFN-treated cells is controlled by 2'5'-linked oligoadenylate (2-5A)-dependent RNase (RNase L), a uniquely regulated endoribonuclease that requires short 5'-phosphorylated, 2-5A for its activity. Because RNase L is also implicated in the regulation of cell proliferation, we monitored its expression in colorectal adenocarcinomas and noncancerous polyps from familial adenomatous polyposis patients. Elevated levels of RNase L mRNA and activity were found in 17 of 20 tumors compared with corresponding normal mucosa. An mAb against RNase L revealed elevated amounts of this RNase in sections of the tumors, largely in the base of the villi. The occurrence of elevated levels of RNase L seems to be an early event in colorectal tumorigenesis, suggesting that control of RNA turnover is an important step in tumor progression. These data also indicate that regulating RNase L activity may be a useful strategy in treating colorectal carcinomas.

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