Tumour suppressor function of RNase L in a mouse model.
RNase L is one of the key enzymes involved in the molecular mechanisms of interferon (IFN) actions. Upon binding with its activator, 5'-phosphorylated, 2'-5' oligoadenylates (2-5A), RNase L plays an important role in the antiviral and anti-proliferative functions of IFN, and exerts proapoptotic activity independent of IFN. In this study, we have found that RNase L retards proliferation in an IFN-dependent and independent fashion. To directly measure the effect of RNase L on tumour growth in the absence of other IFN-induced proteins, human RNase L cDNA was stably expressed in P-57 cells, an aggressive mouse fibrosarcoma cell line. Three clonal cell lines were isolated in which the overexpression of RNase L was 15-20-fold of the endogenous level. Groups of five nude mice were injected subcutaneously with either the human RNase L overexpressing clones (P-RL) or control cells transfected with an empty vector (P-Vec). Tumour growth by the two cell lines was monitored by measuring tumour volumes. In the P-RL group, tumour formation was significantly delayed and the tumours grew much slower compared to the control group. Morphologically, the P-RL tumour appeared to have more polygonal cells and increased single cell tumour necrosis. Interestingly, P-RL tumours eventually started to grow. Further analysis revealed, however, that these tumours no longer expressed ectopic RNase L. Our findings suggest that RNase L plays a critical role in the inhibition of fibrosarcoma growth in nude mice.
Liu
Wendy
W
Department of Chemistry, Clinical Chemistry Program, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA.
Liang
Shu-Ling
SL
Liu
Hongli
H
Silverman
Robert
R
Zhou
Aimin
A
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018076:DNA, Complementary / Q000378:metabolism; D004722:Endoribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease