Variation in use of estrogen receptor-α gene promoters in breast cancer compared by quantification of promoter-specific messenger RNA

Toru Higuchi, Tatsuyuki Gohno, Takamasa Nagatomo, Hideaki Tokiniwa, Toshifumi Niwa, Jun Horiguchi, Tetsunari Oyama, Izumi Takeyoshi, Shin Ichi Hayashi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)249-257.e2
JournalClinical Breast Cancer
Volume14
Issue number4
DOIs
Publication statusPublished - 2014 Aug

Keywords

  • Breast cancer tissue
  • Clinicopathological factors
  • Estrogen receptor variants
  • Estrogen receptor-alpha gene
  • Promoter usage

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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