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Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma

Journal Article · · Science (Washington, D.C.); (United States)
; ; ; ; ; ;
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.
Research Organization:
Georgetown Univ. Medical Center, WA (USA)
OSTI ID:
6276625
Journal Information:
Science (Washington, D.C.); (United States), Journal Name: Science (Washington, D.C.); (United States) Vol. 243:4896; ISSN SCIEA
Country of Publication:
United States
Language:
English

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Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL FUNCTIONS
BIOLOGICAL PATHWAYS
CARCINOMAS
CELL CULTURES
CLONE CELLS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
FUNCTIONS
GENE REGULATION
GENES
MAMMALS
MICE
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PHENOTYPE
RADIOSENSITIVITY
RNA
RODENTS
TUMOR CELLS
VERTEBRATES