Silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase-independent pathway.

Abstract:

:Survivin is recognized as an attractive target in cancer therapy because of its selective overexpression in the majority of tumors. Upregulated expression of this protein correlates with increased tumor grade, recurrence risk and decreased cancer patients survival. In this study, we assessed the efficacy of two survivin-specific small interfering RNA (siRNA) constructs to inhibit T47D human breast cancer cell growth. After siRNA transfection, T47D cells showed a significant reduction in proliferation and survival exhibiting clear signs of apoptosis. pSil_1 that targeted exon 1 exhibited a stronger inhibitory effect on cell growth, and increased cell apoptosis compared to pSil_30 that targeted exon 4. Cell apoptosis was found to be mediated by translocation of the mitochondrial apoptosis inducing factor (AIF), while no changes were observed in caspase-3 activation and Bid cleavage. Thus, silencing survivin expression using siRNA strategies represents a suitable therapeutic approach to selectively modulate the survival and growth of human breast cancer cells.

journal_name

J Cell Biochem

authors

Croci DO,Cogno IS,Vittar NB,Salvatierra E,Trajtenberg F,Podhajcer OL,Osinaga E,Rabinovich GA,Rivarola VA

doi

10.1002/jcb.21836

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

381-90

issue

2

eissn

0730-2312

issn

1097-4644

journal_volume

105

pub_type

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