University of Massachusetts Medical School Faculty Publications

Title

IMP3 Protein Promotes Chemoresistance in Breast Cancer Cells by Regulating Breast Cancer Resistance Protein (ABCG2) Expression

UMMS Affiliation

Department of Cancer Biology

Publication Date

5-3-2013

Document Type

Article

Subjects

RNA-Binding Proteins; Breast Neoplasms; Neoplasm Proteins; ATP-Binding Cassette Transporters; Drug Resistance, Neoplasm

Disciplines

Cancer Biology | Neoplasms | Therapeutics

Abstract

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.

Rights and Permissions

Citation: J Biol Chem. 2013 May 3;288(18):12569-73. doi: 10.1074/jbc.C112.442319. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of biological chemistry

PubMed ID

23539627