title: Variation in use of estrogen receptor-α gene promoters in breast cancer compared by quantification of promoter-specific messenger RNA.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Japan; Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University, Maebashi, Japan. Electronic address: m11702025@gunma-u.ac.jp.
authors: Toru
authors: T
authors: Higuchi
authors: Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors: Tatsuyuki
authors: T
authors: Gohno
authors: Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors: Takamasa
authors: T
authors: Nagatomo
authors: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors: Hideaki
authors: H
authors: Tokiniwa
authors: Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors: Toshifumi
authors: T
authors: Niwa
authors: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors: Jun
authors: J
authors: Horiguchi
authors: Department of Diagnostic Pathology, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors: Tetsunari
authors: T
authors: Oyama
authors: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University, Maebashi, Japan.
authors: Izumi
authors: I
authors: Takeyoshi
authors: Department of Molecular and Functional Dynamics, Graduate School of Medicine, Tohoku University, Sendai, Japan; Center for Regulatory Epigenome and Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors: Shin-ichi
authors: S
authors: Hayashi
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger
keywords: Breast cancer tissue; Clinicopathological factors; Estrogen receptor variants; Estrogen receptor-alpha gene; Promoter usage