Transforming growth factor-beta 1 induces apoptosis in gastric cancer cells through a p53-independent pathway.
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.
Yamamoto
M
M
Cancer Center of Kyushu University Hospital, Fukuoka, Japan.
Maehara
Y
Y
Sakaguchi
Y
Y
Kusumoto
T
T
Ichiyoshi
Y
Y
Sugimachi
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001483:Base Sequence; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011509:Proteoglycans; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II