RRC ID 62954
著者 Gaowa S, Futamura M, Tsuneki M, Kamino H, Tajima JY, Mori R, Arakawa H, Yoshida K.
タイトル Possible role of p53/Mieap-regulated mitochondrial quality control as a tumor suppressor in human breast cancer.
ジャーナル Cancer Sci
Abstract Mitochondria-eating protein (Mieap), encoded by a p53-target gene, plays an important role in mitochondrial quality control (MQC). Mieap has been reported to have a critical role in tumor suppression in colorectal cancer. Here, we investigated its role as a tumor suppressor in breast cancer. The enforced expression of exogenous Mieap in breast cancer cells induced caspase-dependent apoptosis, with activation of both caspase-3/7 and caspase-9. Immunohistochemistry revealed endogenous Mieap in the cytoplasm in 24/75 (32%) invasive ductal carcinomas (IDC), 15/27 (55.6%) cases of ductal carcinoma in situ (DCIS) and 16/18 (88.9%) fibroadenomas (FA) (IDC vs DCIS; P = 0.0389, DCIS vs FA; P = 0.0234, IDC vs FA; P < 0.0001). In IDC, the Mieap promoter was methylated in 6/46 (13%) cases, whereas p53 was mutated in 6/46 (13%) cases. Therefore, the p53/Mieap-regulated MQC pathway was inactivated in 12/46 IDC (26.1%). Interestingly, all tumors derived from the 12 patients with Mieap promoter methylation or p53 mutations pathologically exhibited more aggressive and malignant breast cancer phenotypes. Impairment of p53/Mieap-regulated MQC pathway resulted in significantly shorter disease-free survival (DFS) (P = 0.021), although p53 status is more prognostic in DFS than Mieap promoter methylation. These results indicate that p53/Mieap-regulated MQC has a critical role in tumor suppression in breast cancer, possibly in part through mitochondrial apoptotic pathway.
巻・号 109(12)
ページ 3910-3920
公開日 2018-12-1
DOI 10.1111/cas.13824
PMID 30290054
PMC PMC6272104
MeSH Adult Aged Aged, 80 and over Apoptosis Breast Neoplasms / genetics Breast Neoplasms / metabolism* Carcinoma, Ductal, Breast / genetics Carcinoma, Ductal, Breast / metabolism* Caspases / metabolism Cell Line, Tumor Cytoplasm / metabolism DNA Methylation Disease-Free Survival Female Gene Expression Regulation, Neoplastic Humans MCF-7 Cells Middle Aged Mitochondria / metabolism Mitochondrial Proteins / genetics* Mitochondrial Proteins / metabolism* Mutation Promoter Regions, Genetic Tumor Suppressor Protein p53 / genetics* Tumor Suppressor Protein p53 / metabolism*
IF 4.966
リソース情報
ヒト・動物細胞 MKN1(RCB1003) MKN7(RCB0999) MKN45(RCB1001) MKN74(RCB1002) Kato III(RCB2088) SH-10-TC(RCB1940) TE-5(RCB1949) TE-4(RCB2097) TE-10(RCB2099)