Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta I

PTEN is a candidate tumour suppressor gene and frequently mutated in multiple cancers, however, not in pancreatic cancer. Recently, it has been demonstrated that PTEN expression is regulated by TGF-βI. Using TGF-βI transgenic mice (n=7) and wildtype littermates (n=6), as well as pancreatic tissues obtained from organ donors (n=10) and patients with pancreatic cancer (n=10), we assessed the expression of PTEN by means of immunohistochemistry and semiquantitative PCR analysis. In addition, PANC-I cells were treated with TGF-βI in vitro and the levels of PTEN mRNA were determined in these cells. In human pancreatic cancers PTEN mRNA levels were significantly decreased (P<0.05). In addition, in the pancreas of TGF-βI transgenic mice the expression of PTEN was significantly reduced (P<0.01), as compared to wildtype littermates and incubation of PANC-I cells with TGF-βI decreased PTEN mRNA levels after 24 h. Inasmuch as TGF-βI decreases PTEN expression in human pancreatic cancer cells and human pancreatic cancers overexpress TGF-βI, the reduced expression of PTEN in pancreatic cancer may be mediated by TGF-βI overexpression. Thus, although PTEN is not mutated in pancreatic cancers, the reduction of its expression may give pancreatic cancer cells an additional growth advantage.