Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and comedo necrosis

It is well known that comedo necrosis is closely associated with an aggressive phenotype of ductal carcinoma in situ ( DCIS ) of human breast, but its molecular mechanisms remain largely unclear. Therefore, in this study, we first examined the gene expression profile of comedo DCIS based on microarray data and identified CYC 1 as a gene associated with comedo necrosis. Cytochrome c1 ( CYC 1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production. However, the significance of CYC 1 has not yet been examined in DCIS . We therefore immunolocalized CYC 1 in 47 DCIS cases. CYC1 immunoreactivity was detected in 40% of DCIS cases, and the immunohistochemical CYC 1 status was significantly associated with tumor size, nuclear grade, comedo necrosis, van Nuys classification, and Ki‐67 labeling index. Subsequent in vitro studies indicated that CYC 1 was significantly associated with mitochondrial membrane potential in MCF 10 DCIS .com DCIS cells. Moreover, CYC 1 significantly promoted proliferation activity of MCF 10 DCIS .com cells and the cells transfected with CYC 1 si RNA decreased pro‐apoptotic caspase 3 activity under hypoxic or anoxic conditions. Considering that the center of DCIS is poorly oxygenated, these results indicate that CYC 1 plays important roles in cell proliferation and comedo necrosis through the elevated oxidative phosphorylation activity in human DCIS .