Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces α9-nicotinic acetylcholine receptor expression in human breast cancer cells

Chia Hwa Lee, Ya Chieh Chang, Ching Shyang Chen, Shih Hsin Tu, Ying Jan Wang, Li Ching Chen, Yu Jia Chang, Po Li Wei, Hui Wen Chang, Chien Hsi Chang, Ching Shui Huang, Chih Hsiung Wu, Yuan Soon Ho

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47 Citations (Scopus)


The primary aim of this study was to elucidate the role of the estrogen receptor (ER), a transcription factor involved in the nicotine- and 17β-estradiol (E2)-mediated up-regulation of α9-nAChR gene expression. A real-time polymerase chain reaction (PCR) assay was used to quantify the α9-nAChR mRNA expression levels of surgically isolated (n = 339) and laser-capture microdissected tissues (ER+ versus ER-, n = 6 per group). Chromatin immunoprecipitation (ChIP) and luciferase-promoter activity assays were used to investigate the ER-mediated transcriptional regulation of α9-nAChR gene expression. We observed that breast tumors with higher α9-nAChR mRNA expression levels (i.e., a mean fold ratio in the tumor/normal-paired samples of greater than tenfold) were associated with the lowest 5-year disease-specific survival rate (50%, dead/alive = 4/4, total = 8 patients, P = 0.006), in contrast to breast tumors with low levels (i.e., a mean fold ratio of less than onefold) of α9-nAChR expression (88%, dead/alive = 3/22, total = 25 patients). Furthermore, higher α9-nAChR mRNA expression levels were preferentially detected in ER+ tumor tissues in comparison to ER- tumor tissues (ER+ versus ER- patients: n = 160 vs. 72; mean fold ratios of α9-nAChR expression = 11 ± 3 vs. 6.7 ± 2.3 fold, respectively). In vitro promoter-binding assays demonstrated that the ER is a major transcription factor that mediates nicotine- and E2-induced up-regulation of α9-nAChR gene expression in MCF-7 cells. In conclusion, our data indicate that the ER plays a central role in mediating α9-nAChR gene up-regulation in response to either nicotine or E2 stimulation.

Original languageEnglish
Pages (from-to)331-345
Number of pages15
JournalBreast Cancer Research and Treatment
Issue number2
Publication statusPublished - Sep 2011



  • AP1
  • Breast cancer
  • Estrogen
  • Estrogen receptor
  • Nicotine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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