Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1

• Published in: British journal of cancer 2002-01, Vol.86 (2), p.257-262
• Main Authors: Ebert, MPA, Fei, G, Schandl, L, Mawrin, C, Dietzmann, K, Herrera, P, Friess, H, Gress, T M, Malfertheiner, P
• Format: Article
• Language: English
• ISSN: 0007-0920
• DOI: 10.1038/sj/bjc/6600031

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- beta 1. Using TGF- beta 1 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-1 cells were treated with TGF- beta 1 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- beta 1 transgenic mice the expression of PTEN was significantly reduced (P < 0.01), as compared to wildtype littermates and incubation of PANC-1 cells with TGF- beta 1 decreased PTEN mRNA levels after 24 h. Inasmuch as TGF- beta 1 decreases PTEN expression in human pancreatic cancer cells and human pancreatic cancers overexpress TGF- beta 1, the reduced expression of PTEN in pancreatic cancer may be mediated by TGF- beta 1 overexpression. Thus, although PTEN is not mutated in pancreatic cancers, the reduction of its expression may give pancreatic cancer cells an additional growth advantage.