TRANSFORMING GROWTH-FACTOR-BETA-1 INDUCES APOPTOSIS IN GASTRIC-CANCERCELLS THROUGH A P53 INDEPENDENT PATHWAY

BACKGROUND. Apoptosis is induced by various anticancer agents or radia tion through the tumor suppressor gene p53-dependent pathway and is al so 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 exam ined 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 bl ot analysis and the reverse transcriptase-polymerase chain reaction an alysis, respectively. RESULTS. Of 12 cell lines, wild-type p53 was pre sent 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 o f 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 canc er cells through TGF-beta receptors I and II and a p53-independent pat hway. (C) 1996 American Cancer Society.