title: Cytochrome c1 in ductal carcinoma in situ of breast associated with proliferation and comedo necrosis.
abstract: 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 MCF10DCIS.com DCIS cells. Moreover, CYC1 significantly promoted proliferation activity of MCF10DCIS.com 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.
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Chishiki
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.|Department of Surgery, Osaki Citizen Hospital, Osaki, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ebata
authors.affiliation: Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shibahara
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Pathology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takashi
authors.identifier: http://orcid.org/0000-0003-0195-815X
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology*; D003575:Cytochromes c1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D061346:Laser Capture Microdissection; D008875:Middle Aged; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D003575:Cytochromes c1
keywords: 
  DCIS
  ; CYC1; Comedo necrosis; immunohistochemistry; proliferation