scholarly journals Caspase-10 Sensitizes Breast Carcinoma Cells to TRAIL-Induced but Not Tumor Necrosis Factor-Induced Apoptosis in a Caspase- 3-Dependent Manner

2005 ◽  
Vol 25 (7) ◽  
pp. 2808-2818 ◽  
Author(s):  
Ingo H. Engels ◽  
Gudrun Totzke ◽  
Ute Fischer ◽  
Klaus Schulze-Osthoff ◽  
Reiner U. Jänicke
Keyword(s):  
Breast Carcinoma ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Breast Carcinoma Cells ◽  
Induced Apoptosis ◽  
Necrosis Factor ◽  
Mcf 7

ABSTRACT Although signaling by death receptors involves the recruitment of common components into their death-inducing signaling complexes (DISCs), apoptosis susceptibility of various tumor cells to each individual receptor differs quite dramatically. Recently it was shown that, besides caspase-8, caspase-10 is also recruited to the DISCs, but its function in death receptor signaling remains unknown. Here we show that expression of caspase-10 sensitizes MCF-7 breast carcinoma cells to TRAIL- but not tumor necrosis factor (TNF)-induced apoptosis. This sensitization is most obvious at low TRAIL concentrations or when apoptosis is assessed at early time points. Caspase-10-mediated sensitization for TRAIL-induced apoptosis appears to be dependent on caspase-3, as expression of caspase-10 in MCF-7/casp-3 cells but not in caspase-3-deficient MCF-7 cells overcomes TRAIL resistance. Interestingly, neutralization of TRAIL receptor 2 (TRAIL-R2), but not TRAIL-R1, impaired apoptosis in a caspase-10-dependent manner, indicating that caspase-10 enhances TRAIL-R2-induced cell death. Furthermore, whereas processing of caspase-10 was delayed in TNF-treated cells, TRAIL triggered a very rapid activation of caspase-10 and -3. Therefore, we propose a model in which caspase-10 is a crucial component during TRAIL-mediated apoptosis that in addition actively requires caspase-3. This might be especially important in systems where only low TRAIL concentrations are supplied that are not sufficient for the fast recruitment of caspase-8 to the DISC.

scholarly journals LIGHT, a Member of the Tumor Necrosis Factor Ligand Superfamily, Prevents Tumor Necrosis Factor-α-mediated Human Primary Hepatocyte Apoptosis, but Not Fas-mediated Apoptosis

2002 ◽  
Vol 277 (51) ◽  
pp. 50054-50061 ◽  
Author(s):  
Hideki Matsui ◽  
Yukiko Hikichi ◽  
Isamu Tsuji ◽  
Takao Yamada ◽  
Yasushi Shintani
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Time Course ◽  
Caspase 3 ◽  
Nuclear Factor Κb ◽  
Caspase 8 ◽  
Death Domain ◽  
Human Primary Hepatocytes ◽  
Induced Apoptosis ◽  
Necrosis Factor

LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its receptors have been identified as lymphotoxin-β receptor (LTβR) and the herpesvirus entry mediator (HVEM)/ATAR/TR2, both of which lack the cytoplasmic sequence termed the “death domain.” The present study has demonstrated that LIGHT inhibits TNFα-mediated apoptosis of human primary hepatocytes sensitized by actinomycin D (ActD), but not Fas- or TRAIL-mediated apoptosis. Furthermore, LIGHT does not prevent some cell lines such as HepG2 or HeLa from undergoing ActD/TNFα-induced apoptosis. This protective effect requires LIGHT pretreatment at least 3 h prior to ActD sensitization. LIGHT stimulates nuclear factor-κB (NF-κB)-dependent transcriptional activity in human hepatocytes like TNFα. The time course of NF-κB activation after LIGHT administration is similar to that of the pretreatment required for the anti-apoptotic effect of LIGHT. LIGHT inhibits caspase-3 processing on the apoptotic protease cascade in TNFα-mediated apoptosis but not Fas-mediated apoptosis. In addition, increased caspase-3 and caspase-8 activities in ActD/TNFα-treated cells are effectively blocked by LIGHT pretreatment. However, LIGHT does not change the expression of TNFRp55, TNFRp75, and Fas. These results indicate that LIGHT may act as an anti-apoptotic agent against TNFα-mediated liver injury by blocking the activation of both caspase-3 and caspase-8.

scholarly journals Krüppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens

2012 ◽  
Vol 19 (6) ◽  
pp. 741-750 ◽  
Author(s):  
Kiyoshi Takagi ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
Yasuhiro Nakamura ◽  
Takanori Ishida ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Breast Carcinoma ◽  
Carcinoma Cells ◽  
Human Breast Carcinoma ◽  
Dependent Manner ◽  
Breast Carcinomas ◽  
Human Breast ◽  
Breast Carcinoma Cells ◽  
Mcf 7

Krüppel-like factor 5 (intestinal) or Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor and involved in important biological processes including cell proliferation and differentiation. However, clinical significance of KLF5 protein has remained largely unknown in breast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinoma cases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, and median value of the ratio of KLF5-positive carcinoma cells was 30% and was positively associated with the status of androgen receptor. KLF5 immunoreactivity was also significantly associated with increased risk of recurrence and worse clinical outcome in breast cancer patients by univariate analyses, and subsequent multivariate analyses demonstrated that KLF5 immunoreactivity was an independent prognostic factor for both disease-free and breast cancer-specific survival of the patients. We then examined possible regulation of KLF5 by androgen using MCF-7 breast carcinoma cells. KLF5 mRNA was induced by biologically active androgen 5α-dihydrotestosterone in a dose- and time-dependent manner in MCF-7 cells. In addition, results of transfection experiments demonstrated that proliferation activity of MCF-7 cells was significantly associated with the KLF5 expression level. These findings suggest that KLF5 is an androgen-responsive gene in human breast carcinomas and play important roles in the progression of breast carcinomas. KLF5 immunoreactivity is therefore considered a potent prognostic factor in human breast cancers.

scholarly journals Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent

2002 ◽  
Vol 9 (6) ◽  
pp. 636-642 ◽  
Author(s):  
R Ofir ◽  
R Seidman ◽  
T Rabinski ◽  
M Krup ◽  
V Yavelsky ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Caspase 3 ◽  
Carcinoma Cells ◽  
Caspase 9 ◽  
Breast Carcinoma Cells ◽  
Induced Apoptosis
Sign in / Sign up

Export Citation Format

Share Document