Transforming growth factor-β1 induces apoptosis in gastric cancer cells through a p53-independent pathway

✍ Scribed by Manabu Yamamoto; Yoshihiko Maehara; Yoshihisa Sakaguchi; Tetsuya Kusumoto; Yuji Ichiyoshi; Keizo Sugimachi

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 579 KB
• Volume: 77
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/(sici)1097-0142(19960415)77:8<1628::aid-cncr31>3.0.co;2-#

✦ Synopsis

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-PI (TGF-0,). In this study, the authors investigated whether TGF-0, would induce apoptosis in gastrointestinal cancer cells, and its relation to the status of the p53 gene.

METHODS.

The induction of apoptosis by TGF-P, 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-PI mRNA and TGF receptors I and 11 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-PI was expressed in all 12 lines, but both TGF receptors I and I1 were expressed in only 6 lines. Addition of TGF-0, induced DNA ladder formation only in KATOIII cells, with deleted p53 mRNA, but expressed TGF receptors I and 11.

CONCLUSIONS.

These findings show that TGF-P, induces apoptosis in gastric cancer cells through TGF-8 receptors I and I1 and a p53-independent pathway.