Variation in Use of Estrogen Receptor-α Gene Promoters in Breast Cancer Compared by Quantification of Promoter-Specific Messenger RNA

Estrogen receptor (ER)-alpha has multiple promoters upstream of the transcriptional start points in its gene. We examined the promoter usage of 43 ER alpha-positive breast cancer tissue samples and found the promoters to be used at similar ratios. The usage of ER alpha promoters may be important for development, differentiation, or carcinogenesis. Introduction: Estrogen receptor (ER)-alpha expression offers a critical characterization of breast cancer, but risk of recurrence is difficult to predict using only ER alpha status. The ER alpha gene has at least 6 transcription start sites, 6 distinct first exons, and probably 6 promoters. To examine whether these promoters have differential effects in breast cancer, we quantified expression of promoter-specific ER alpha messenger RNA (mRNA), using real-time polymerase chain reaction (PCR) and statistical assessment. Patients and Methods: We examined variations in the use of breast cancer cell lines and 43 ER alpha positive (ER alpha(+)) breast cancer tissue samples by quantifying promoter-specific mRNA of ER alpha with real-time PCR analysis using primers and probes specially designed for this study. Moreover, we correlated the results of quantified the promoter-specific mRNA with mRNA of total ER alpha and related them to clinicopathological factors statistically. We also examined multiregression analyses for promoter-specific mRNAs of ER alpha. Result: We found the promoters to be used at almost similar ratios among ER alpha(+) breast cancer cell lines and ER alpha(+) breast cancer tissues. Clinicopathological variations were associated with identical ER alpha promoter choices. When we examined the contribution of mRNA from 3 promoters in breast cancer tissues to total ER alpha using multiple regression analysis, we found that only promoter A showed a significant (P < .05) transcript coefficient. Conclusion: Our findings imply that the use of ER alpha promoters as prognostic biomarkers is unfeasible. However, our results suggest that promoter usage of ER alpha may contribute to its expression in normal development and differentiation of individual or carcinogenesis of breast cancer.