Cell Death and Survival MTBP Is Overexpressed in Triple-Negative Breast Cancer and Contributes to Its Growth and Survival

Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer commonly resistant to therapeutics that have been successful in increasing survival in patients with estrogen receptor–positive (ERþ) and HER2þ breast cancer. As such, identifying factors that contribute to poor patient outcomes andmediate the growth and survival of TNBC cells remain important areas of investigation. MTBP (MDM2-binding protein), a gene linked to cellular proliferation and a transcriptional target of the MYC oncogene, is overexpressed in human malignancies, yet its contribution to cancer remains unresolved. Evaluation of mRNA expression and copy number variation data from The Cancer Genome Atlas (TCGA) revealed thatMTBP is commonly overexpressed in breast cancer and 19% show amplification of MTBP. Increased transcript or gene amplification of MTBP significantly correlated with reduced breast cancer patient survival. Further analysis revealed that while MTBP mRNA is overexpressed in both ERþ and HER2þ breast cancers, its expression is highest in TNBC. MTBP mRNA and protein levels were also significantly elevated in a panel of humanTNBC cell lines. Knockdown ofMTBP in TNBC cells induced apoptosis and significantly reduced TNBC cell growth and soft agar colony formation, which was rescued by expression of shRNA-resistantMtbp.Notably, inducible knockdown ofMTBP expression significantly impaired TNBC tumor growth, in vivo, including in established tumors. Thus, these data emphasize thatMTBP is important for the growth and survival of TNBC and warrants further investigation as a potential novel therapeutic