TGFβ-induced growth inhibition involves cell cycle inhibitor p21 and pRb independent from p15 expression

It is generally assumed that TGF beta 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 TGF beta-induced negative growth control in spite of the loss of p15 and p16 expression. In these cell lines, TGF beta-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 TGF beta-induced growth inhibition. Moreover, overexpression of p21 in the p21-deficient cell line Pane Tu1 leads to growth arrest. Thus, TGF beta-induced growth control correlates with p21 expression and pRb status independent of p15 and/or p16 expression.