title: Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1.
abstract: 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-beta1. Using TGF-beta1 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-beta1 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-beta1 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-beta1 decreased PTEN mRNA levels after 24 h. Inasmuch as TGF-beta1 decreases PTEN expression in human pancreatic cancer cells and human pancreatic cancers overexpress TGF-beta1, the reduced expression of PTEN in pancreatic cancer may be mediated by TGF-beta1 overexpression. Thus, although PTEN is not mutated in pancreatic cancers, the reduction of its expression may give pancreatic cancer cells an additional growth advantage.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipzigerstr. 44, D-39120 Magdeburg, Germany. Matthias.Ebert@medizin.uni-magdeburg.de
authors.forename: M P A
authors.initials: MP
authors.lastname: Ebert
authors.forename: G
authors.initials: G
authors.lastname: Fei
authors.forename: L
authors.initials: L
authors.lastname: Schandl
authors.forename: C
authors.initials: C
authors.lastname: Mawrin
authors.forename: K
authors.initials: K
authors.lastname: Dietzmann
authors.forename: P
authors.initials: P
authors.lastname: Herrera
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: T M
authors.initials: TM
authors.lastname: Gress
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human