Research

QBCF Strategic Grants Program

Research Factsheet

PROFESSOR MICHEL LEBEL*

CENTRE DE RECHERCHE EN CANCÉROLOGIE, CENTRE HOSPITALIER UNIVERSITAIRE DE QUEBEC, QUÉBEC

PROJET TITLE Identification of protein partners required for YB-1 to confer chemoresistance in breast tumors.

PRINCIPAL INVESTIGATOR Prof. Michel Lebel

INSTITUTE Centre de recherche de l’Hôtel-Dieu de Québec, Université Laval

TOTAL RESEARCH BUDGET $58,500

NON-SCIENTIFIC SUMMARY*:

YB-1 is a member of a family of DNA-binding proteins containing a cold shock domain. In recent years, several laboratories have demonstrated that YB-1 is directly involved in the cellular response to genotoxic stress. Upon cisplatin treatments, YB-1 translocates from the cytoplasm to the nucleus. Interestingly, YB-1 is increased in tumor cultured cell lines resistant to cisplatin. In fact, several studies have indicated that the level of nuclear expression of YB-1 is predictive of drug resistance and patient outcome in breast and ovarian cancers. Recently, we have observed that YB-1 activates the DNA repair enzyme hNTH1 upon cisplatin treatments. All these observations suggest that YB-1 is directly involved in DNA repair and is important in conferring drug resistance of tumor cells. Additional data indicates that overexpression of YB-1 in tumor cells generates several chemoresistance signatures apparent by microarray expression analyses.

The principal objective of this project is to identify proteins associated with YB-1 in cisplatin resistance and to isolate small interference RNAs against these YB-1 protein partners to potentiate cisplatin treatments. The understanding of the molecules through which YB-1 confers drug resistance in tumor cells, will allow us

to design better strategies (or new therapeutic drugs) to control cancer progression.

QBCF-CRS Joint Grant Program September 1, 2008 – August 31, 2010.

* The Cancer Research Society and the Quebec Breast Cancer Foundation are co-financing this project.