Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death.

Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death. Research Abstract Details 

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Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death. Abstract Text:

Franck Meslin,Ahmed ,Ping Gao,Abdelali Jalil,Nathalie Cahuzac,Salem Chouaib,Maryam Mehrpour,

We investigated the relationship between the resistance to the proapoptotic action of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and cellular prion protein (PrPc) function, using the TRAIL-sensitive MCF-7 human breast adenocarcinoma cell line and two TRAIL-resistant sublines: 2101 and MCF-7/ADR. All of the cell lines tested expressed TRAIL-R1 and TRAIL-R2. TRAIL decoy receptors were not detected, suggesting that the resistance of 2101 and MCF-7/ADR cells, strongly expressing PrPc, to TRAIL-mediated cell death was independent from the expression of TRAIL receptors and death-inducing signaling complex formation. Down-regulation of PrPc by small interfering RNA increased the sensitivity of Adriamycin- and TRAIL-resistant cells to TRAIL, but not to epirubicin/Adriamycin. TRAIL-mediated apoptosis in PrPc knocked-down cells was associated with caspase processing, Bid cleavage, and Mcl-1 degradation. In addition, an increased sensitivity of apoptosis-resistant cells to TRAIL after PrPc silencing was not associated with the increased recruitment of receptors and intracellular signaling molecule to the death-inducing signaling complex. Bcl-2 expression was substantially decreased after PrPc knock-down but the levels of Bcl-X(L) and Mcl-1 were not affected. The down-regulation of Bcl-2 was concomitant with Bax delocalization. Our findings support the notion that silencing of PrPc facilitates the activation of proapoptotic Bax by down-regulation of Bcl-2 expression, thereby abolishing the resistance of breast cancer cells to TRAIL-induced apoptosis.

Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death. Publishing Authors By Initials

F Meslin,A ,P Gao,A Jalil,N Cahuzac,S Chouaib,M Mehrpour,

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Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 67

Page Numbers: 10910-9

Journal Abbreviation: Cancer Res.

ISSN: 1538-7445

DAY: 15

MONTH: Nov

YEAR: 2007

Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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Grant and Affiliation Information for Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death.

AFFILIATION: INSERM U753, Laboratoire d'Immunologie des Tumeurs Humaines, Interaction Effecteurs Cytotoxiques-Système Tumoral, Institut Gustave Roussy PR1 and IFR 54, Villejuif, France.

Country: United States

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MEDLINETA: Cancer Res

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