title: miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer.
abstract: Expression levels of estrogen receptor (ER) alpha govern estrogen-dependent growth, response to endocrine therapy, and prognosis in ERalpha-positive breast cancer. Multiple mechanisms involved in altering ERalpha gene expression in breast cancer have been identified, including ERalpha gene amplification as well as transcriptional silencing by DNA methylation of CpG islands within the ERalpha promoter and mutations within the open reading frame of ERalpha. However, expression levels of ERalpha in breast cancer tissues differ widely among patients, and frequently change during disease progression and in response to systemic therapies. Recent evidence has shown that microRNA mutations or misexpression correlate with various human cancers, and miR-206 is reported to decrease endogenous ERalpha mRNA and protein levels in human MCF-7 breast cancer cells via two specific target sites within the 3'-untranslated region of the human ERalpha transcript. In this study, we show for the first time that miR-206 expression is markedly decreased in ERalpha-positive human breast cancer tissues assayed by quantitative reverse transcription-PCR analysis. Moreover, we observe that miR-206 expression is inversely correlated with ERalpha but not ERbeta mRNA expression in breast cancer tissues. Transfection experiments revealed that introduction of miR-206 into estrogen-dependent MCF-7 breast cancer cells inhibits cell growth in a dose- and time-dependent manner. Our results suggest that miR-206 could be a novel candidate for endocrine therapy that targets only ERalpha in breast cancer.
authors.affiliation: Oncology, Immunology, and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kondo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D035683:MicroRNAs; D012333:RNA, Messenger; C522220:mirn206 microRNA, rat