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. 1996 Apr 15;77(8 Suppl):1628-33.
doi: 10.1002/(SICI)1097-0142(19960415)77:8<1628::AID-CNCR31>3.0.CO;2-#.

Transforming growth factor-beta 1 induces apoptosis in gastric cancer cells through a p53-independent pathway

M Yamamoto  1 , Y Maehara, Y Sakaguchi, T Kusumoto, Y Ichiyoshi, K Sugimachi
Affiliations

Transforming growth factor-beta 1 induces apoptosis in gastric cancer cells through a p53-independent pathway

M Yamamoto et al. Cancer. .

Abstract

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-beta 1 (TGF-beta 1). In this study, the authors investigated whether TGF-beta 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-beta 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-beta 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-beta 1 was expressed in all 12 lines, but both TGF receptors I and II were expressed in only 6 lines. Addition of TGF-beta 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-beta 1 induces apoptosis in gastric cancer cells through TGF-beta receptors I and II and a p53-independent pathway.

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