Fibroblast growth factor-4 enhanced G2 arrest and cell survival following ionizing radiation.
Fibroblast growth factors (FGFs) bind to cell membrane receptors and activate signal transduction pathways related to cell growth, angiogenesis, and tumorigenesis. FGFs have been shown to be abundantly expressed in some of the human tumors, which are known to be poorly responsive to radiation therapy. Using adrenal cortical carcinoma cells genetically engineered to express FGF-4, we have tested cellular survival following exposure to ionizing radiation. We report here that FGF-4 enhances cellular capacity to survive ionizing radiation. Furthermore, cell cycle analysis shows a pronounced increase in the duration of G2 arrest, suggesting perturbation of a cell cycle checkpoint. These findings implicate fibroblast growth factor-mediated signal transduction in cellular resistance of human tumors to radiation therapy.
Jung
M
M
Department of Radiation Medicine, Vincent T. Lombardi Comprehensive Cancer Research Center, Georgetown University School of Medicine, Washington, DC 20007.
Kern
F G
FG
Jorgensen
T J
TJ
McLeskey
S W
SW
Blair
O C
OC
Dritschilo
A
A
D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D014407:Tumor Cells, Cultured
C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors