Does Estrogen Receptor Alpha (ESR1) Specific MicroRNAs Expression Correlate with ESR1 Transcript Levels in Breast Cancer?
M Nassiri, S Salardini, C Reyes, S Ramos, J Olczyk, M Nadji, FA Tavassoli. Indiana University School of Medicine, Indianapolis, IN; Yale University School of Medicine, New Haven, CT; University of Miami, Miami, FL
Background: Molecular mechanisms behind down-regulation of estrogen receptor in breast cancer are not well known. Recently estrogen receptor alpha (ESR1) specific microRNAs (miRNA) have been identified. MicroRNAs have a regulatory effect on their target genes . We analyzed expression of miRNAs that target ESR1 in breast cancer samples.
Design: Different morphologically recognized subtypes of breast cancer were evaluated: apocrine (n=7), metaplastic (n=14), medullary (n=14), tubular (n=6), lobular (n=6), ER positive IDC (n=24) and ER negative IDC (n=15). Immunohistochemistry for ER alpha, AR, P63, GCFP was performed to validate the morphologic subtypes. RNA was isolated from microdissected tumor cells from the paraffin embedded blocks. Real-time PCR was performed for ESR1 and three ESR1-specfic miRNA; has-mir-7d, 22 and 206. RPL2, GAPDH and PPIA were used as control housekeeping genes.
Results: hsa-mir-7d and 22 had significantly lower expression level in ER positive compared to ER negative tumors. hsa-mir 206 was rarely expressed in ER positive breast cancer. Although ESR-1 transcript copy number was significantly different between ER negative and ER positive tumors it didn't show a quantitative correlation with miRNA level.
Conclusions: ESR1 specific miRNAs are more often expressed and show a higher transcript copies in ER negative breast cancers. They might contribute to down-regulation of estrogen receptor in ER negative breast cancers.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 12, Wednesday Morning