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

Ebert MP, Fei G, Schandl L, Mawrin C, Dietzmann K, Herrera P, Friess H, Gress TM, Malfertheiner P - Br. J. Cancer (2002)

Bottom Line: Recently, it has been demonstrated that PTEN expression is regulated by TGF-beta1.In addition, PANC-1 cells were treated with TGF-beta1 in vitro and the levels of PTEN mRNA were determined in these cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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Immunohistochemical analysis of PTEN expression in pancreatic cancer. (A) In human pancreatic cancers PTEN immunoreactivity was present in some of the cancer cells. (B) Sections incubated with the anti-PTEN antibody and the blocking peptide exhibited no PTEN immunoreactivity.
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fig1: Immunohistochemical analysis of PTEN expression in pancreatic cancer. (A) In human pancreatic cancers PTEN immunoreactivity was present in some of the cancer cells. (B) Sections incubated with the anti-PTEN antibody and the blocking peptide exhibited no PTEN immunoreactivity.

Mentions: The presence of human PTEN was assessed using paraffin-embedded tissue sections obtained from 10 patients with pancreatic cancer undergoing pancreatic surgery. The human tissues were fixed in Bouin's solution and paraffin embedded. The anti-PTEN antibody (n-19) is an affinity-purified goat polyclonal antibody raised against a peptide mapping at the amino-terminus of human PTEN and was used at a dilution of 1:800 (Santa Cruz, CA, USA) (Steck et al, 1997; Sano et al, 1999). In addition, sections were also incubated with the anti-PTEN antibody C-20, which is a goat polyclonal antibody raised against a peptide mapping at the carboxy-terminus of human PTEN (Santa Cruz, CA, USA). Paraffin sections (4 μm thick) were deparaffinized and rehydrated. For negative controls, the primary antibodies were omitted and/or preimmune serum was used. Furthermore, the anti-PTEN antibody n-19 was also incubated with its respective blocking peptide which resulted in no specific immunoreactivity in the immunohistochemical analysis, demonstrating the specificity of the anti-PTEN antibody (Figure 1Figure 1


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

Ebert MP, Fei G, Schandl L, Mawrin C, Dietzmann K, Herrera P, Friess H, Gress TM, Malfertheiner P - Br. J. Cancer (2002)

Immunohistochemical analysis of PTEN expression in pancreatic cancer. (A) In human pancreatic cancers PTEN immunoreactivity was present in some of the cancer cells. (B) Sections incubated with the anti-PTEN antibody and the blocking peptide exhibited no PTEN immunoreactivity.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2375189&req=5

fig1: Immunohistochemical analysis of PTEN expression in pancreatic cancer. (A) In human pancreatic cancers PTEN immunoreactivity was present in some of the cancer cells. (B) Sections incubated with the anti-PTEN antibody and the blocking peptide exhibited no PTEN immunoreactivity.
Mentions: The presence of human PTEN was assessed using paraffin-embedded tissue sections obtained from 10 patients with pancreatic cancer undergoing pancreatic surgery. The human tissues were fixed in Bouin's solution and paraffin embedded. The anti-PTEN antibody (n-19) is an affinity-purified goat polyclonal antibody raised against a peptide mapping at the amino-terminus of human PTEN and was used at a dilution of 1:800 (Santa Cruz, CA, USA) (Steck et al, 1997; Sano et al, 1999). In addition, sections were also incubated with the anti-PTEN antibody C-20, which is a goat polyclonal antibody raised against a peptide mapping at the carboxy-terminus of human PTEN (Santa Cruz, CA, USA). Paraffin sections (4 μm thick) were deparaffinized and rehydrated. For negative controls, the primary antibodies were omitted and/or preimmune serum was used. Furthermore, the anti-PTEN antibody n-19 was also incubated with its respective blocking peptide which resulted in no specific immunoreactivity in the immunohistochemical analysis, demonstrating the specificity of the anti-PTEN antibody (Figure 1Figure 1

Bottom Line: Recently, it has been demonstrated that PTEN expression is regulated by TGF-beta1.In addition, PANC-1 cells were treated with TGF-beta1 in vitro and the levels of PTEN mRNA were determined in these cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

Show MeSH
Related in: MedlinePlus