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Transforming growth factor‐β1 induces apoptosis in gastric cancer cells through a p53‐independent pathway
Author(s) -
Yamamoto Manabu,
Maehara Yoshihiko,
Sakaguchi Yoshihisa,
Kusumoto Tetsuya,
Ichiyoshi Yuji,
Sugimachi Keizo
Publication year - 1996
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19960415)77:8+<1628::aid-cncr7>3.0.co;2-9
Subject(s) - medicine , apoptosis , cancer research , transforming growth factor , cancer , growth factor , cancer cell , p53 protein , oncology , genetics , biology , immunohistochemistry , receptor
BACKGROUND Apoptosis is induced by various anticancer agents or radiation through the tumor suppressor gene p53‐dependent pathway and is also induced by other factors, including transforming growth factor‐β 1 (TGF‐β 1 ). In this study, the authors investigated whether TGF‐β 1 would induce apoptosis in gastrointestinal cancer cells, and its relation to the status of the p53 gene. METHODS The induction of apoptosis by TGF‐β 1 was determined in 12 gastrointestinal cancer cell lines using DNA ladder formation. Status of the p53 gene was examined by sequencing of cDNA from p53 mRNA and expressions of TGF‐β 1 mRNA and TGF receptors I and II mRNAs were determined by Northern blot analysis and the reverse transcriptase‐polymerase chain reaction analysis, respectively. RESULTS Of 12 cell lines, wild‐type p53 was present in 3 lines, point mutation was detected in 7 lines, and p53 mRNA was absent in 2 lines. TGF‐β 1 was expressed in all 12 lines, but both TGF receptors I and II were expressed in only 6 lines. Addition of TGF‐β 1 induced DNA ladder formation only in KATOIII cells, with deleted p53 mRNA, but expressed TGF receptors I and II. CONCLUSIONS These findings show that TGF‐β 1 induces apoptosis in gastric cancer cells through TGF‐β receptors I and II and a p53‐independent pathway. Cancer 1996;77:1628‐33.