Overexpression of ubiquitous mitochondrial creatine kinase (uMtCK) accelerates tumor growth by inhibiting apoptosis of breast cancer cells and is associated with a poor prognosis in breast cancer patients

• Published in: Biochemical and biophysical research communications 2012-10, Vol.427 (1), p.60-66
• Main Authors: Qian, Xiao-Long, Li, Ya-Qing, Gu, Feng, Liu, Fang-Fang, Li, Wei-Dong, Zhang, Xin-Min, Fu, Li
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Apoptosis; Biomarkers, Tumor - biosynthesis; Breast cancer; Breast Neoplasms - enzymology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cell crowding; Creatine Kinase, Mitochondrial Form - biosynthesis; Female; Humans; Mice; Middle Aged; Neoplasm Transplantation; Prognosis; Survival Analysis; Ubiquitous mitochondrial creatine kinase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.08.147

► uMtCK expression is associated with a poor prognosis in breast cancer (BCa). ► uMtCK inhibits apoptosis when BCa cells are crowded in culture. ► uMtCK inhibits apoptosis by suppressing the mitochondrial apoptotic pathway. ► Animal model studies suggest uMtCK expression promotes tumor progression in BCa. Ubiquitous mitochondrial creatine kinase (uMtCK), a mitochondrial isoenzyme of creatine kinase (CK), is a central controller of cellular energy homeostasis. Overexpression of uMtCK has been reported to be associated with a poor prognosis for several tumors. The aim of this study was to assess its association with breast cancer (BCa) and to further investigate its underlying mechanisms. We first detected uMtCK expression by immunohistochemistry in human BCa tissues and assessed the association with the prognosis of patients. We then evaluated uMtCK expression in crowded and normal condition cultures of several human BCa cell lines. After two stable clones of the MDA-MB-231 cell line with high expression of uMtCK were established, cell growth, apoptosis and mitochondrial apoptotic pathway protein expression were measured in these clones. Finally, tumorigenicity of the above cells was assessed using nude mice to explore the relationship between uMtCK expression and tumor progression. uMtCK expression was detected in 85.5% (47 of 55) of the invasive ductal carcinomas of breast tissue, not otherwise specified (IDC-NOS). Expression in BCa tissue was significantly associated with reduced progression-free survival (PFS; P=0.019) and overall survival (OS; P=0.022) of the patients. Up-regulation of uMtCK expression was identified in crowded BCa cells in culture, and the number of apoptotic cells was significantly decreased in uMtCK transfected MDA-MB-231 cell clones (P