Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung carcinoma.
In this study we examined the radiation survival response of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells (BEAS-2B) stably transfected with c-raf-1 and/or c-myc. C-raf-1 transfectants (2B-raf), and c-raf-1 and c-myc double transfectants (2B-raf/myc) were relatively radioresistant compared with c-myc (2B-myc) or control vector transfectants (2B-neo) (2B-raf, D0 = 2.445 Gy; 2B-raf/myc, D0 = 2.46 Gy; 2B-myc, D0 = 1.501 Gy; 2B-neo, D0 = 2.029 Gy). The steady state level of superoxide dismutase (SOD) mRNA was higher in radioresistant cells (2B-raf and 2B-raf/myc). In addition, 2B-raf but not 2B-raf/myc or 2B-myc transfectants revealed relatively higher number of cells in G2+M phase of the cell cycle. These findings present experimental evidence that Raf-1 expression correlates with the radiation-resistant response of 2B-raf or 2B-raf/myc transfectants and suggest a role of SOD in Raf-1-associated radiation resistance. Because 2B-raf transfectants are non-tumorigenic, and double transfectants (2B-raf/myc) are tumorigenic with some phenotypic traits found in small-cell lung carcinomas, our data imply a dissociation between the Raf-1-mediated mechanisms of radiation protection and progression of lung neoplasia.
Pfeifer
A
A
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Mark
G
G
Leung
S
S
Dougherty
M
M
Spillare
E
E
Kasid
U
U
D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D002453:Cell Cycle / Q000235:genetics; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D010641:Phenotype; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013482:Superoxide Dismutase; D019908:Proto-Oncogene Proteins c-raf