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

Estrogen receptor (ER)-a has multiple promoters upstream of the transcriptional start points in its gene. We examined the promoter usage of 43 ERa-positive breast cancer tissue samples and found the promoters to be used at similar ratios. The usage of ERa promoters may be important for development, differentiation, or carcinogenesis. Introduction: Estrogen receptor (ER)-a expression offers a critical characterization of breast cancer, but risk of recurrence is difficult to predict using only ERa status. TheERa 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 ERa 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 ERa positive (ERa þ ) breast cancer tissue samples by quantifying promoter-specific mRNA of ERa 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 ERa and related them to clinicopathological factors sta- tistically. We also examined multiregression analyses for promoter-specific mRNAs of ERa. Result: We found the promoters to be used at almost similar ratios among ERa þ breast cancer cell lines and ERa þ breast cancer tissues. Clinicopathological variations were associated with identical ERa promoter choices. When we examined the contri- bution of mRNA from 3 promoters in breast cancer tissues to total ERa 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 ERa promoters as prognostic biomarkers is unfeasible. However, our results suggest that promoter usage of ERa may contribute to its expression in normal development and differentiation of individual or carcinogenesis of breast cancer.