Radiosensitivity of human breast cancer cells transduced with wild-type p53 gene is influenced by the p53 status of parental cells.
Induction of apoptosis with chemotherapeutic agents or radiation in tumours is frequently related to the status of those p53 gene of the tumours. To examine whether forced expression of the wild-type p53 gene in tumour cells can modulate their susceptibility to radiation and anti-cancer agents, we retrovirally transduced two types of human breast cancer cell lines, which respectively harboured a mutated p53 gene (OCUB-M) or wild-type p53 gene (YMB-1), with the wild-type p53 gene. Transduced cells which consistently expressed the wild-type p53 gene (OCUB-M/p53, YMB-1/p53) proliferated at the same rate as control cells which were transduced with the beta-galactosidase gene (OCUB-M/lacz, YMB-1/lacz). However, sensitivity to radiation was increased in OCUB-M/p53 cells but not in YMB-1/p53 cells. In vitro chemosensitivity to DNA-damaging anticancer agents such as cyclophosphamide and 5-fluorouracil was not influenced by the transduction of the wild-type p53 gene in either cells. Expression of the wild-type p53 gene in p53-mutated human breast cancer cells can therefore increase their sensitivity to radiation but not their chemosensitivity. Therapeutic effects following by the transduction of the wild-type p53 gene were not observed in breast cancer cells already bearing the wild-type p53 gene.
Maeda
T
T
Department of Sugery (II), Chiba University, School of Medicine, Japan.
Matsubara
H
H
Koide
Y
Y
Sugaya
M
M
Miyazawa
Y
Y
Tasaki
K
K
Isono
K
K
Ochiai
T
T
Sakiyama
S
S
Tagawa
M
M
D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D003520:Cyclophosphamide / Q000633:toxicity; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000633:toxicity; D016158:Genes, p53; D005822:Genetic Vectors; D006801:Humans; D007700:Kinetics; D016296:Mutagenesis; D011836:Radiation Tolerance; D011994:Recombinant Proteins / Q000378:metabolism; D012190:Retroviridae; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D016662:Virus Integration
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D003520:Cyclophosphamide; D005472:Fluorouracil