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

Mayuko Chishiki, Kiyoshi Takagi, Ai Sato, Yasuhiro Miki, Yuta Yamamoto, Akiko Ebata, Yukiko Shibahara, Mika Watanabe, Takanori Ishida, Hironobu Sasano, Takashi Suzuki

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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 CYC1 as a gene associated with comedo necrosis. Cytochrome c1 (CYC1) is a subunit of complex III in the mitochondrial oxidative phosphorylation that is involved in energy production. However, the significance of CYC1 has not yet been examined in DCIS. We therefore immunolocalized CYC1 in 47 DCIS cases. CYC1 immunoreactivity was detected in 40% of DCIS cases, and the immunohistochemical CYC1 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 CYC1 was significantly associated with mitochondrial membrane potential in DCIS cells. Moreover, CYC1 significantly promoted proliferation activity of cells and the cells transfected with CYC1 siRNA decreased pro-apoptotic caspase 3 activity under hypoxic or anoxic conditions. Considering that the center of DCIS is poorly oxygenated, these results indicate that CYC1 plays important roles in cell proliferation and comedo necrosis through the elevated oxidative phosphorylation activity in human DCIS.

Original languageEnglish
Pages (from-to)1510-1519
Number of pages10
JournalCancer Science
Issue number7
Publication statusPublished - 2017 Jul


  • Comedo necrosis
  • CYC1
  • DCIS
  • immunohistochemistry
  • proliferation


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