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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 .

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