Journal
ENDOCRINE-RELATED CANCER
Volume 20, Issue 1, Pages 91-102Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-12-0207
Keywords
breast cancer; microRNA; estrogen receptor; miR-1290
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Funding
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [24791387, 23591902] Funding Source: KAKEN
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Recent analyses have identified heterogeneity in estrogen receptor alpha (ER alpha)-positive breast cancer. Subtypes called luminal A and luminal B have been identified, and the tumor characteristics, such as response to endocrine therapy and prognosis, are different in these subtypes. However, little is known about how the biological characteristics of ER-positive breast cancer are determined. In this study, expression profiles of microRNAs (miRNAs) and mRNAs in ER-positive breast cancer tissue were compared between ERhigh Ki67(low) tumors and ERlow Ki67(high) tumors by miRNA and mRNA microarrays. Unsupervised hierarchical clustering analyses revealed distinct expression patterns of miRNAs and mRNAs in these groups. We identified a downregulation of miR-1290 in ERhigh Ki67(low) tumors. Among 11 miRNAs that were upregulated in ERhigh Ki67(low) tumors, quantitative RT-PCR detection analysis using 64 samples of frozen breast cancer tissue identified six miRNAs (let-7a, miR-15a, miR-26a, miR-34a, miR-193b, and miR-342-3p). We picked up 11 genes that were potential target genes of the selected miRNAs and that were differentially expressed in ERhigh Ki67(low) tumors and ERlow Ki67(high) tumors. Protein expression patterns of the selected target genes were analyzed in 256 ER-positive breast cancer samples by immunohistochemistry: miR-1290 and its putative targets, BCL2, FOXA1, MAPT, and NAT1, were identified. Transfection experiments revealed that introduction of miR-1290 into ER-positive breast cancer cells decreased expression of NAT1 and FOXA1. Our results suggest that miR-1290 and its potential targets might be associated with characteristics of ER-positive breast cancer.
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