TY - JOUR
T1 - MTBP is overexpressed in triple-negative breast cancer and contributes to its growth and survival
AU - Grieb, Brian C.
AU - Chen, Xi
AU - Eischen, Christine M.
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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 (ER+) and HER2+breast cancer. As such, identifying factors that contribute to poor patient outcomes and mediate 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 ofmRNA expression and copy number variation data from The Cancer Genome Atlas (TCGA) revealed that MTBP 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 ER+and HER2+breast cancers, its expression is highest in TNBC. MTBP mRNA and protein levels were also significantly elevated in a panel of human TNBCcell lines. Knockdown of MTBP inTNBC cells induced apoptosis and significantly reduced TNBC cell growth and soft agar colony formation, which was rescued by expression of shRNA-resistant Mtbp. Notably, inducible knockdown of MTBP expression significantly impaired TNBC tumor growth, in vivo, including in established tumors. Thus, these data emphasize that MTBP is important for the growth and survival of TNBC and warrants further investigation as a potential novel therapeutic target.
AB - 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 (ER+) and HER2+breast cancer. As such, identifying factors that contribute to poor patient outcomes and mediate 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 ofmRNA expression and copy number variation data from The Cancer Genome Atlas (TCGA) revealed that MTBP 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 ER+and HER2+breast cancers, its expression is highest in TNBC. MTBP mRNA and protein levels were also significantly elevated in a panel of human TNBCcell lines. Knockdown of MTBP inTNBC cells induced apoptosis and significantly reduced TNBC cell growth and soft agar colony formation, which was rescued by expression of shRNA-resistant Mtbp. Notably, inducible knockdown of MTBP expression significantly impaired TNBC tumor growth, in vivo, including in established tumors. Thus, these data emphasize that MTBP is important for the growth and survival of TNBC and warrants further investigation as a potential novel therapeutic target.
UR - http://www.scopus.com/inward/record.url?scp=84907271995&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907271995&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-14-0069
DO - 10.1158/1541-7786.MCR-14-0069
M3 - Article
C2 - 24866769
AN - SCOPUS:84907271995
VL - 12
SP - 1216
EP - 1224
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 9
ER -