Expression of wild-type p53 gene confers increased sensitivity to radiation and chemotherapeutic agents in human esophageal carcinoma cells.
The status of the p53 gene of tumor cells can modify the sensitivity of the tumors to radiation and anti-cancer agents. Human esophageal cancer cells (T.Tn) bearing mutated p53 gene were retrovirally transduced with wild-type p53 gene. The transduced cells (T.Tn/p53) which stably expressed wild-type p53 proliferated at the same rate as parental cells. However, the sensitivity to radiation was significantly improved by the transduction and T.Tn/p53 cells became markedly susceptible to cisplatin and etoposide compared with parental cells. Administration of cisplatin noticeably suppressed the growth of T.Tn/p53 tumors but not T.Tn tumors inoculated in nude mice. Forced expression of wild-type p53 gene thereby can increase the sensitivity to DNA damage in esophageal cells.
Matsubara
H
H
Department of Surgery (II), School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Kimura
M
M
Sugaya
M
M
Koide
Y
Y
Gunji
Y
Y
Takegana
K
K
Asano
T
T
Ochiai
T
T
Isono
K
K
Sakiyama
S
S
Tagawa
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009368:Neoplasm Transplantation; D011836:Radiation Tolerance; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D002945:Cisplatin