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Science 10 March 1989:
Vol. 243. no. 4896, pp. 1354 - 1356
DOI: 10.1126/science.2466340
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Articles
Science, Vol 243, Issue 4896, 1354-1356
Copyright © 1989 by American Association for the Advancement of Science
Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma
U Kasid,
A Pfeifer,
T Brennan,
M Beckett,
RR Weichselbaum,
A Dritschilo,
and
GE Mark
Department of Radiation Medicine, Vincent T. Lombardi Comprehensive Cancer Research Center, Georgetown University Medical Center, Washington 20007.
Antisense RNA-mediated inhibition of gene expression was used to investigate the biological function of the c-raf-1 gene in a radiation-resistant human squamous carcinoma cell line, SQ-20B. S1 nuclease protection assays revealed that transfection of full-length raf complementary DNA in the antisense orientation (AS) leads to a specific reduction (greater than tenfold) of steady-state levels of the endogenous c-raf-1 sense (S) transcript in SQ-20B cells. In nude mice, the malignant potential of SQ-20B cells transfected with raf (S) was significantly increased relative to that of SQ-20B cells transfected with raf (AS). SQ-20B cells containing transfected raf (S) maintained a radiation-resistant phenotype as compared to those cells harboring the AS version, which appeared to have enhanced radiation sensitivity. These data indicate that the reduced expression of endogenous c-raf-1 is sufficient to modulate the tumorigenicity and the radiation-resistant phenotype of SQ-20B cells, thus implicating c-raf-1 in a pathway important to the genesis of this type of cancer.
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