TGFbeta-induced growth inhibition involves cell cycle inhibitor p21 and pRb independent from p15 expression.
It is generally assumed that TGFbeta induces cell cycle arrest through the cooperative action of cell cycle inhibitors p15, p27 and p21. Here, we found that several pancreatic carcinoma cell lines exert TGFbeta-induced negative growth control in spite of the loss of p15 and p16 expression. In these cell lines, TGFbeta-induced growth control correlates with the upregulation of the p21 protein and active pRb expression. Conversely, cells without p21 and/or pRb expression are resistant to TGFbeta -induced growth inhibition. Moreover, overexpression of p21 in the p21-deficient cell line Panc Tu1 leads to growth arrest. Thus, TGFbeta-induced growth control correlates with p21 expression and pRb status independent of p15 and/or p16 expression.
Voss
M
M
Universitatsklinikum Kiel, Abteilung Thoraxchirurgie und Allgemeine Chirurgie, 24105 Kiel, Germany.
Wolff
B
B
Savitskaia
N
N
Ungefroren
H
H
Deppert
W
W
Schmiegel
W
W
Kalthoff
H
H
Naumann
M
M
D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D016193:G1 Phase; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology; D016160:Retinoblastoma Protein / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006131:Growth Inhibitors; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins