Elevated levels of 2',5'-linked oligoadenylate-dependent ribonuclease L occur as an early event in colorectal tumorigenesis.
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.
Wang
L
L
Departments of Cancer Biology, Urology, and Colorectal Surgery, Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Zhou
A
A
Vasavada
S
S
Dong
B
B
Nie
H
H
Church
J M
JM
Williams
B R
BR
Banerjee
S
S
Silverman
R H
RH
D000230:Adenocarcinoma / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000201:enzymology*; D004722:Endoribonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007417:Intestinal Polyps / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease