Cytochrome c1 as a favorable prognostic marker in estrogen receptor-positive breast carcinoma.

BACKGROUND:Cytochrome c1 (CYC1) is a heme-containing subunit of mitochondria complex III and is mainly involved in cellular energy production. A recent study has demonstrated that CYC1 was overexpressed in breast carcinoma tissues and induced proliferation, migration and invasion of estrogen receptor (ER)-negative breast carcinoma cells. However, the clinical significance of CYC1 protein remains largely unclear in invasive breast carcinoma, and biological functions of CYC1 have not been reported in ER-positive breast carcinoma cells. MATERIALS AND METHODS:We immunolocalized CYC1 in 172 invasive breast carcinomas and evaluated its clinical significance according to the ER-status. Subsequently, we examined the effects of CYC1 on proliferation, glycolysis and chemosensitivity to paclitaxel, which is one of the most common chemotherapeutic agents in breast cancer, in ER-positive breast carcinoma cells (MCF7 and T47D). RESULTS:CYC1 immunoreactivity was detected in 47% of ER-positive cases and 30% of ER-negative cases. Immunohistochemical CYC1 status was inversely associated with Ki67 in ER-positive cases, and it was a significantly favorable prognostic factor for both disease-free and breast cancer-specific survival of the patients. On the other hand, no significant association was detected between CYC1 status and clinicopathological factors in ER-negative cases. In in vitro experiments, MCF7 and T47D cells transfected specific siRNA for CYC1 significantly increased cell proliferation activity, L-lactate production and cell viability after paclitaxel treatment. CONCLUSION:These results suggest that CYC1 inhibits cell proliferation, glycolytic activity and increases chemosensitivity to paclitaxel in ER-positive breast carcinoma cells and that CYC1 status is a potent favorable prognostic factor in ER-positive breast cancer patients.

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