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Differential induction of apoptosis by tumor necrosis factor-related apoptosis-inducing ligand in human ovarian carcinoma cells.
Gynecol Oncol. 2004 Jun; 93(3):594-604.GO

Abstract

OBJECTIVES

In this study, we examine the sensitivity of a panel of ovarian carcinoma cells, which includes four primary ovarian cancer cell samples, and four normal ovarian epithelium samples to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We also examine the intracellular regulation of TRAIL-mediated apoptosis.

METHODS

The sensitivity to TRAIL was determined by short-term survival assays on seven ovarian carcinoma cell lines, four primary samples of ovarian cancer, and four normal ovarian epithelium samples. We assessed the activation of the apoptotic pathway in TRAIL-resistant and -sensitive tumor cells. The expression of TRAIL receptors was determined by flow cytometry. The protein expression of FADD, XIAP, caspase-8, caspase-3, BAX, and c-FLIP were determined by immunoblot analyses.

RESULTS

We show that ovarian cancer cells display variable sensitivity to TRAIL-induced apoptosis although most cell lines have similar sensitivity to cisplatin. Normal ovarian epithelium samples were mostly sensitive to TRAIL. In sensitive cells, TRAIL induced caspase-8-dependent apoptosis, which subsequently led to activation of caspase-3. Both sensitive and resistant cells expressed caspase-8, caspase-3, FADD, XIAP, and c-FLIP at similar levels. A significant enhancement in cell death was observed in TRAIL-resistant cells when c-FLIP(L) levels were downregulated by RNA interference.

CONCLUSIONS

These data suggest that sensitivity to TRAIL and chemotherapy does not necessarily correlate in human ovarian cancer cells. Cancerous cells isolated from patients with ovarian cancer show variable sensitivity to TRAIL but most normal ovarian epithelial cells are sensitive. In human ovarian cancer cells, c-FLIP(L) may participate to the regulation of the TRAIL signaling cascade.

Authors+Show Affiliations

Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001 Sherbrooke, Canada J1H 5N1.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15196850

Citation

Lane, Denis, et al. "Differential Induction of Apoptosis By Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Human Ovarian Carcinoma Cells." Gynecologic Oncology, vol. 93, no. 3, 2004, pp. 594-604.
Lane D, Cartier A, L'Espérance S, et al. Differential induction of apoptosis by tumor necrosis factor-related apoptosis-inducing ligand in human ovarian carcinoma cells. Gynecol Oncol. 2004;93(3):594-604.
Lane, D., Cartier, A., L'Espérance, S., Côté, M., Rancourt, C., & Piché, A. (2004). Differential induction of apoptosis by tumor necrosis factor-related apoptosis-inducing ligand in human ovarian carcinoma cells. Gynecologic Oncology, 93(3), 594-604.
Lane D, et al. Differential Induction of Apoptosis By Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Human Ovarian Carcinoma Cells. Gynecol Oncol. 2004;93(3):594-604. PubMed PMID: 15196850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential induction of apoptosis by tumor necrosis factor-related apoptosis-inducing ligand in human ovarian carcinoma cells. AU - Lane,Denis, AU - Cartier,Andréanne, AU - L'Espérance,Sylvain, AU - Côté,Marceline, AU - Rancourt,Claudine, AU - Piché,Alain, PY - 2003/08/26/received PY - 2004/6/16/pubmed PY - 2004/7/28/medline PY - 2004/6/16/entrez SP - 594 EP - 604 JF - Gynecologic oncology JO - Gynecol Oncol VL - 93 IS - 3 N2 - OBJECTIVES: In this study, we examine the sensitivity of a panel of ovarian carcinoma cells, which includes four primary ovarian cancer cell samples, and four normal ovarian epithelium samples to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We also examine the intracellular regulation of TRAIL-mediated apoptosis. METHODS: The sensitivity to TRAIL was determined by short-term survival assays on seven ovarian carcinoma cell lines, four primary samples of ovarian cancer, and four normal ovarian epithelium samples. We assessed the activation of the apoptotic pathway in TRAIL-resistant and -sensitive tumor cells. The expression of TRAIL receptors was determined by flow cytometry. The protein expression of FADD, XIAP, caspase-8, caspase-3, BAX, and c-FLIP were determined by immunoblot analyses. RESULTS: We show that ovarian cancer cells display variable sensitivity to TRAIL-induced apoptosis although most cell lines have similar sensitivity to cisplatin. Normal ovarian epithelium samples were mostly sensitive to TRAIL. In sensitive cells, TRAIL induced caspase-8-dependent apoptosis, which subsequently led to activation of caspase-3. Both sensitive and resistant cells expressed caspase-8, caspase-3, FADD, XIAP, and c-FLIP at similar levels. A significant enhancement in cell death was observed in TRAIL-resistant cells when c-FLIP(L) levels were downregulated by RNA interference. CONCLUSIONS: These data suggest that sensitivity to TRAIL and chemotherapy does not necessarily correlate in human ovarian cancer cells. Cancerous cells isolated from patients with ovarian cancer show variable sensitivity to TRAIL but most normal ovarian epithelial cells are sensitive. In human ovarian cancer cells, c-FLIP(L) may participate to the regulation of the TRAIL signaling cascade. SN - 0090-8258 UR - https://www.unboundmedicine.com/medline/citation/15196850/Differential_induction_of_apoptosis_by_tumor_necrosis_factor_related_apoptosis_inducing_ligand_in_human_ovarian_carcinoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090825804002008 DB - PRIME DP - Unbound Medicine ER -