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Title

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

Authors
Ebert, M. P.
Fei, G.
Schandl, L.
Mawrin, C.
Dietzmann, K.
Friess, H.
Gress, T. M.
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Published in British Journal of Cancer. 2002, vol. 86, no. 2, p. 257-262
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.
Keywords AnimalsGene Expression Regulation, NeoplasticHumansImmunohistochemistryMiceMice, TransgenicPTEN PhosphohydrolasePancreatic Neoplasms/ genetics/pathologyPhosphoric Monoester Hydrolases/ biosynthesis/pharmacologyPolymerase Chain ReactionRNA, Messenger/analysisTransforming Growth Factor beta/ biosynthesisTransforming Growth Factor beta1Tumor Suppressor Proteins/ biosynthesis/pharmacology
Identifiers
PMID: 11870516
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EBERT, M. P. et al. Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1. In: British Journal of Cancer, 2002, vol. 86, n° 2, p. 257-262. https://archive-ouverte.unige.ch/unige:8733

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Deposited on : 2010-07-12

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