IMP3 Protein Promotes Chemoresistance in Breast Cancer Cells by Regulating Breast Cancer Resistance Protein (ABCG2) Expression
Department of Cancer Biology
RNA-Binding Proteins; Breast Neoplasms; Neoplasm Proteins; ATP-Binding Cassette Transporters; Drug Resistance, Neoplasm
Cancer Biology | Neoplasms | Therapeutics
IMP3, a member of a family of insulin-like growth factor II (IGF-II) mRNA-binding proteins (IMPs), is expressed preferentially in triple-negative breast cancers, which are resistant to many chemotherapeutics. However, the mechanisms by which it impacts breast cancer have not been elucidated. We hypothesized a role for IMP3 in chemoresistance based on these observations. Depletion of IMP3 expression in triple-negative breast cancer cells increased their sensitivity to doxorubicin and mitoxantrone significantly but not to taxol. Given that doxorubicin and mitoxantrone are effluxed by breast cancer resistance protein (BCRP), we assessed whether IMP3 regulates BCRP. The data obtained demonstrate that IMP3 binds to BCRP mRNA and regulates BCRP expression. These findings are significant because they provide insight into the mechanism by which IMP3 contributes to aggressive cancers, and they highlight the potential for targeting this mRNA-binding protein for the clinical management of cancer.
DOI of Published Version
J Biol Chem. 2013 May 3;288(18):12569-73. doi: 10.1074/jbc.C112.442319. Link to article on publisher's site
The Journal of biological chemistry
Sanjoy, Samanta; Pursell, Bryan M.; and Mercurio, Arthur M., "IMP3 Protein Promotes Chemoresistance in Breast Cancer Cells by Regulating Breast Cancer Resistance Protein (ABCG2) Expression" (2013). University of Massachusetts Medical School Faculty Publications. 32.