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Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells.

Trauzold A, Schmiedel S, Röder C, Tams C, Christgen M, Oestern S, Arlt A, Westphal S, Kapischke M, Ungefroren H, Kalthoff H - Br. J. Cancer (2003)

Bottom Line: Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype.Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines.Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology, Clinic for General Surgery, UK-SH, Camus Kiel, Germany.

ABSTRACT
Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour cells. We analysed cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as the expression profile of sixteen apoptosis-relevant proteins in five pancreatic carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated apoptosis. Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines. Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive.

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Immunoblot detection of proteins of the IAP-family in pancreatic tumour cells. Protein extracts (30 μg) of pancreatic tumour cells were separated by 12% SDS–PAGE, blotted onto PVDF membranes and the expression of c-IAP2, XIAP and Survivin was analysed using specific antibodies. In parallel, β-actin expression was determined in all lanes. Representative results of three independent experiments are shown.
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fig5: Immunoblot detection of proteins of the IAP-family in pancreatic tumour cells. Protein extracts (30 μg) of pancreatic tumour cells were separated by 12% SDS–PAGE, blotted onto PVDF membranes and the expression of c-IAP2, XIAP and Survivin was analysed using specific antibodies. In parallel, β-actin expression was determined in all lanes. Representative results of three independent experiments are shown.

Mentions: Here we show that the most resistant PancTuI cells expressed strongly elevated levels of c-IAP2, XIAP and Survivin (Figure 5Figure 5


Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells.

Trauzold A, Schmiedel S, Röder C, Tams C, Christgen M, Oestern S, Arlt A, Westphal S, Kapischke M, Ungefroren H, Kalthoff H - Br. J. Cancer (2003)

Immunoblot detection of proteins of the IAP-family in pancreatic tumour cells. Protein extracts (30 μg) of pancreatic tumour cells were separated by 12% SDS–PAGE, blotted onto PVDF membranes and the expression of c-IAP2, XIAP and Survivin was analysed using specific antibodies. In parallel, β-actin expression was determined in all lanes. Representative results of three independent experiments are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2394395&req=5

fig5: Immunoblot detection of proteins of the IAP-family in pancreatic tumour cells. Protein extracts (30 μg) of pancreatic tumour cells were separated by 12% SDS–PAGE, blotted onto PVDF membranes and the expression of c-IAP2, XIAP and Survivin was analysed using specific antibodies. In parallel, β-actin expression was determined in all lanes. Representative results of three independent experiments are shown.
Mentions: Here we show that the most resistant PancTuI cells expressed strongly elevated levels of c-IAP2, XIAP and Survivin (Figure 5Figure 5

Bottom Line: Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype.Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines.Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology, Clinic for General Surgery, UK-SH, Camus Kiel, Germany.

ABSTRACT
Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour cells. We analysed cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as the expression profile of sixteen apoptosis-relevant proteins in five pancreatic carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated apoptosis. Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines. Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive.

Show MeSH
Related in: MedlinePlus