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Sensitivity of prostate cells to TRAIL-induced apoptosis increases with tumor progression: DR5 and caspase 8 are key players.
Prostate. 2006 Jun 15; 66(9):987-95.P

Abstract

BACKGROUND

As advanced prostate cancers are resistant to currently available chemotherapies, we evaluated the cytotoxic effect of TNF-related apoptosis-inducing ligand (TRAIL) and characterized the involvement of its five receptors DR4, DR5, DcR1, DcR2, and osteoprotegerin (OPG) and of the death-inducing signaling complex (DISC)-forming proteins caspase 8 and c-FLIP in prostate cell lines.

METHODS

We used six prostate cell lines, each corresponding to a particular stage in prostate tumorigenesis, and analyzed TRAIL sensitivity in relation to TRAIL receptors' expression.

RESULTS

TRAIL sensitivity was correlated with tumor progression and DR5 expression levels and apoptosis was exclusively mediated by DR5. DcR2 was significantly more abundant in tumor cells than in non-neoplastic ones and may contribute to partial resistance to TRAIL in some prostate tumor cells. Conversely, non-tumoral cells secreted high levels of OPG, which can protect them from apoptosis. Finally, caspase 8 expression levels were as DR5 directly correlated to TRAIL sensitivity in prostate tumor cells.

CONCLUSION

TRAIL-induced apoptosis is closely related to the balanced expression of its different receptors in prostate cancer cells and their modulation could be of potential clinical value for advanced tumor treatment.

Authors+Show Affiliations

GERHM-INSERM U625, IFR140 GFAS, Université de Rennes I, Rennes cedex, France.No affiliation info availableNo 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

16541419

Citation

Hesry, Vincent, et al. "Sensitivity of Prostate Cells to TRAIL-induced Apoptosis Increases With Tumor Progression: DR5 and Caspase 8 Are Key Players." The Prostate, vol. 66, no. 9, 2006, pp. 987-95.
Hesry V, Piquet-Pellorce C, Travert M, et al. Sensitivity of prostate cells to TRAIL-induced apoptosis increases with tumor progression: DR5 and caspase 8 are key players. Prostate. 2006;66(9):987-95.
Hesry, V., Piquet-Pellorce, C., Travert, M., Donaghy, L., Jégou, B., Patard, J. J., & Guillaudeux, T. (2006). Sensitivity of prostate cells to TRAIL-induced apoptosis increases with tumor progression: DR5 and caspase 8 are key players. The Prostate, 66(9), 987-95.
Hesry V, et al. Sensitivity of Prostate Cells to TRAIL-induced Apoptosis Increases With Tumor Progression: DR5 and Caspase 8 Are Key Players. Prostate. 2006 Jun 15;66(9):987-95. PubMed PMID: 16541419.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitivity of prostate cells to TRAIL-induced apoptosis increases with tumor progression: DR5 and caspase 8 are key players. AU - Hesry,Vincent, AU - Piquet-Pellorce,Claire, AU - Travert,Marion, AU - Donaghy,Ludovic, AU - Jégou,Bernard, AU - Patard,Jean-Jacques, AU - Guillaudeux,Thierry, PY - 2006/3/17/pubmed PY - 2006/7/6/medline PY - 2006/3/17/entrez SP - 987 EP - 95 JF - The Prostate JO - Prostate VL - 66 IS - 9 N2 - BACKGROUND: As advanced prostate cancers are resistant to currently available chemotherapies, we evaluated the cytotoxic effect of TNF-related apoptosis-inducing ligand (TRAIL) and characterized the involvement of its five receptors DR4, DR5, DcR1, DcR2, and osteoprotegerin (OPG) and of the death-inducing signaling complex (DISC)-forming proteins caspase 8 and c-FLIP in prostate cell lines. METHODS: We used six prostate cell lines, each corresponding to a particular stage in prostate tumorigenesis, and analyzed TRAIL sensitivity in relation to TRAIL receptors' expression. RESULTS: TRAIL sensitivity was correlated with tumor progression and DR5 expression levels and apoptosis was exclusively mediated by DR5. DcR2 was significantly more abundant in tumor cells than in non-neoplastic ones and may contribute to partial resistance to TRAIL in some prostate tumor cells. Conversely, non-tumoral cells secreted high levels of OPG, which can protect them from apoptosis. Finally, caspase 8 expression levels were as DR5 directly correlated to TRAIL sensitivity in prostate tumor cells. CONCLUSION: TRAIL-induced apoptosis is closely related to the balanced expression of its different receptors in prostate cancer cells and their modulation could be of potential clinical value for advanced tumor treatment. SN - 0270-4137 UR - https://www.unboundmedicine.com/medline/citation/16541419/Sensitivity_of_prostate_cells_to_TRAIL_induced_apoptosis_increases_with_tumor_progression:_DR5_and_caspase_8_are_key_players_ L2 - https://doi.org/10.1002/pros.20421 DB - PRIME DP - Unbound Medicine ER -