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-β1. Using TGF-β1 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-β1 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-β1 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-β1 decreased PTEN mRNA levels after 24 h. Inasmuch as TGF-β1 decreases PTEN expression in human pancreatic cancer cells and human pancreatic cancers overexpress TGF-β1, the reduced expression of PTEN in pancreatic cancer may be mediated by TGF-β1 overexpression. Thus, although PTEN is not mutated in pancreatic cancers, the reduction of its expression may give pancreatic cancer cells an additional growth advantage.
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Acknowledgements
This study was supported by grants from the Matthias-Lackas-Stiftung and the Land Sachsen-Anhalt awarded to MPA Ebert. L Schandl was supported by the DAAD.
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Ebert, M., Fei, G., Schandl, L. et al. Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1. Br J Cancer 86, 257–262 (2002). https://doi.org/10.1038/sj.bjc.6600031
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DOI: https://doi.org/10.1038/sj.bjc.6600031
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