Back to Search
Start Over
Inhibition of cell growth by transforming growth factor beta 1 is associated with p53-independent induction of p21 in gastric carcinoma cells.
- Source :
-
Japanese journal of cancer research : Gann [Jpn J Cancer Res] 1996 Apr; Vol. 87 (4), pp. 377-84. - Publication Year :
- 1996
-
Abstract
- Cell cycle regulators such as cyclins, cyclin-dependent kinases (cdks) and their inhibitors control the growth of cells. SDI1/CIP1/WAF1/p21 is a potent inhibitor of G1 cdks, whose expression is induced by wild-type p53. To elucidate the mechanism of growth inhibition by transforming growth factor beta 1 (TGFbeta 1), we examined the effect of TGFbeta 1 on the expression of p21, G1 cyclins and cdks by human gastric cancer cell lines. TGFbeta 1 induced p21 expression and subsequently suppressed cdk2 kinase activity, followed by a reduction in phosphorylation of the product of the retinoblastoma tumor suppressor gene in TMK-1 cells, which are responsive to TGFbeta 1. Coimmunoprecipitation analysis demonstrated that TGFbeta 1 increased the level of p21 protein present in complexes with cdk2. In contrast, TGFbeta 1 did not induce p21 in TGFbeta 1-resistant MKN-28 cells. TGFbeta 1 did not affect the levels of p53 mRNA and protein in TMK-1 and MKN-28 cells, which contain mutated p53 genes. These mutated p53 complementary DNAs, when overexpressed, failed to activate transcription from the p21 promoter. Furthermore, TGFbeta 1 caused a reduction in the steady-state level of cyclin A protein concomitantly with inhibition of cdk2 kinase activity in TMK-1 cells. These results suggest that the growth inhibition of tumor cells by TGFbeta 1 is associated with p53-independent induction of p21, subsequent suppression of cdk activity and a decrease in cyclin A protein in TMK-1 cells.
- Subjects :
- Cell Division drug effects
Cyclin E
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases metabolism
Cyclins metabolism
Genes, Retinoblastoma
Humans
Mutation
Phosphorylation
Protein Serine-Threonine Kinases metabolism
RNA, Messenger metabolism
Tumor Cells, Cultured
Adenocarcinoma metabolism
Adenocarcinoma pathology
CDC2-CDC28 Kinases
Cyclins biosynthesis
Stomach Neoplasms metabolism
Stomach Neoplasms pathology
Transforming Growth Factor beta pharmacology
Tumor Suppressor Protein p53 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0910-5050
- Volume :
- 87
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Japanese journal of cancer research : Gann
- Publication Type :
- Academic Journal
- Accession number :
- 8641969
- Full Text :
- https://doi.org/10.1111/j.1349-7006.1996.tb00233.x