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Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1
M P A Ebert1, G Fei, L Schandl
1Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipzigerstr. 44, D-39120 Magdeburg, Germany. Matthias.Ebert@medizin.uni-magdeburg.de
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.
Insights
Reduced PTEN expression in pancreatic cancer may be driven by TGF-beta1. Although PTEN isn't mutated, its decreased expression offers a growth advantage to pancreatic cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- PTEN is a tumor suppressor gene, frequently mutated in various cancers but not typically in pancreatic cancer.
- Recent findings indicate that Transforming Growth Factor-beta1 (TGF-beta1) regulates PTEN expression.
Purpose of the Study:
- To investigate the role of TGF-beta1 in regulating PTEN expression in pancreatic cancer.
- To determine if reduced PTEN expression in pancreatic cancer is mediated by TGF-beta1.
Main Methods:
- Immunohistochemistry and semiquantitative PCR were used to assess PTEN expression in mouse models and human pancreatic tissues.
- PANC-1 cells were treated with TGF-beta1 in vitro to analyze PTEN mRNA levels.
Main Results:
- PTEN mRNA levels were significantly decreased in human pancreatic cancers compared to controls.
- TGF-beta1 transgenic mice showed significantly reduced PTEN expression in pancreatic tissue versus wildtype littermates.
- In vitro, TGF-beta1 treatment decreased PTEN mRNA levels in PANC-1 cells after 24 hours.
Conclusions:
- Overexpression of TGF-beta1 in human pancreatic cancers correlates with reduced PTEN expression.
- Reduced PTEN expression, potentially mediated by TGF-beta1, may contribute to pancreatic cancer cell growth advantage, despite PTEN not being mutated.