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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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Expression of DISC interacting proteins FADD and FLIP in pancreatic tumour cells. Equal amounts of whole cell lysates (30 μg) from each cell line were separated in 4–12% gradient gels and blotted onto PVDF membrane. Subsequently, the expression of FADD and FLIP was detected using specific antibodies. Equal loading of slots was verified by determination of β-actin expression. Data are representative of at least three independent experiments.
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fig3: Expression of DISC interacting proteins FADD and FLIP in pancreatic tumour cells. Equal amounts of whole cell lysates (30 μg) from each cell line were separated in 4–12% gradient gels and blotted onto PVDF membrane. Subsequently, the expression of FADD and FLIP was detected using specific antibodies. Equal loading of slots was verified by determination of β-actin expression. Data are representative of at least three independent experiments.

Mentions: We found that the DISC interacting protein FADD was clearly down-regulated in resistant cells (Figure 3Figure 3


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)

Expression of DISC interacting proteins FADD and FLIP in pancreatic tumour cells. Equal amounts of whole cell lysates (30 μg) from each cell line were separated in 4–12% gradient gels and blotted onto PVDF membrane. Subsequently, the expression of FADD and FLIP was detected using specific antibodies. Equal loading of slots was verified by determination of β-actin expression. Data are representative of at least three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Expression of DISC interacting proteins FADD and FLIP in pancreatic tumour cells. Equal amounts of whole cell lysates (30 μg) from each cell line were separated in 4–12% gradient gels and blotted onto PVDF membrane. Subsequently, the expression of FADD and FLIP was detected using specific antibodies. Equal loading of slots was verified by determination of β-actin expression. Data are representative of at least three independent experiments.
Mentions: We found that the DISC interacting protein FADD was clearly down-regulated in resistant cells (Figure 3Figure 3

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