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.

OLFM4, LY6D and S100A7 as potent markers for distant metastasis in estrogen receptor‐positive breast carcinoma

“…Immunoreactivity of OLFM4 (Figure A), LY6D (Figure B) and S100A7 (Figure C) was detected in the cytoplasm, membrane and both cytoplasm and nucleus of breast carcinoma cells, respectively (left panel in each figure), but it was negative in the stroma or non‐neoplastic mammary glands (right panel in each figure). When the cases that had more than 10% of the positive carcinoma cells were considered positive for OLFM4, LY6D and S100A7 in this study, with the 10% cut‐off value frequently used as a reproducible evaluation, the frequency of immunohistochemical status in the stage IV and stage I‐III cases was 71% and 27% (2.6‐fold) for OLFM4, 14% and 0% for LY6D and 29% and 9% (3.2‐fold) for S100A7, which is consistent with the results of microarray analysis.…”

“…Previous studies demonstrated that S100A7 was highly expressed in the ductal carcinoma in situ (DCIS) with comedo necrosis, and it was involved in transition to invasive breast carcinoma . Very recently, Sakurai et al reported that S100A7 was upregulated by an interaction between breast carcinoma cells and cancer‐associated adipocytes, and S100A7 immunoreactivity was significantly associated with histological grade, stage, lymph node metastasis and worse prognosis for relapse‐free survival of breast carcinoma, although they did not examine stage IV cases.…”

“…Our present results suggest that OLFM4, LY6D and S100A7 immunoreactivity are potent markers for the distant metastasis, including the prediction, in ER-positive breast carcinoma tissues, and these proteins may become important therapeutic targets in ER-positive breast cancer patients. and pancreatic 30 cancer, and OLFM4 promoted S-phase transition in proliferation 31 and it was involved in suppressing apoptosis 32 Previous studies demonstrated that S100A7 was highly expressed in the ductal carcinoma in situ (DCIS) with comedo necrosis 20 , and it was involved in transition to invasive breast carcinoma. 12 Very recently, Sakurai et al 14 reported that S100A7 was upregulated by an interaction between breast carcinoma cells and cancer-associated adipocytes, and S100A7 immunoreactivity was significantly associated with histological grade, stage, lymph node metastasis and worse prognosis for relapse-free survival of breast carcinoma, although they did not examine stage IV cases.…”

“…We next performed immunohistochemistry for the top 3 genes (ie, OLFM4, LY6D and S100A7) in ER-positive breast carcinoma tissues using the first set (n = 18). Immunoreactivity of OLFM4 (Figure 2A), LY6D ( Figure 2B) and S100A7 ( Figure 2C When the cases that had more than 10% of the positive carcinoma cells were considered positive for OLFM4, LY6D and S100A7 in this study, with the 10% cut-off value frequently used as a reproducible evaluation, 20 the frequency of immunohistochemical status in the stage IV and stage I-III cases was 71% and 27% (2.6-fold) for OLFM4, 14% and 0% for LY6D and 29% and 9% (3.2-fold) for S100A7, which is consistent with the results of microarray analysis.…”

Characterizing functional consequences of DNA copy number alterations in breast and ovarian tumors by spaceMap

“…NAPRT has been observed to promote energy status, protein synthesis and cell size in various cancer cells, and NAPRT-dependent NAD+ biosynthesis contributes to cell metabolism as well as DNA repair process, so that NAPRT has been recently suggested to be used to increase the efficacy of NAMPT inhibitors and chemotherapy (Piacente et al, 2017). CYC1 plays important roles in cell proliferation and comedo necrosis through elevating oxidative phosphorylation activities, and has been recently suggested to serve as a biomarker to predict poor prognosis in breast cancer patients (Han et al, 2016; Chishiki et al, 2017). All these are useful pieces of information to help to figure out the functional consequences of the amplification of the CNA-hub on 8q24.23-24.3, which then could lead to detection of novel drug targets or biomarkers for ovarian cancer.…”