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

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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
Volume129
Issue number2
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Nicotinic Receptors
Nicotine
Estrogen Receptors
Estrogens
Breast Neoplasms
Up-Regulation
Gene Expression
Messenger RNA
Transcription Factors
Neoplasms
Chromatin Immunoprecipitation
MCF-7 Cells
Luciferases
Real-Time Polymerase Chain Reaction
Estradiol
Lasers
Survival Rate

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces α9-nicotinic acetylcholine receptor expression in human breast cancer cells. / Lee, Chia Hwa; Chang, Ya Chieh; Chen, Ching Shyang; Tu, Shih Hsin; Wang, Ying Jan; Chen, Li Ching; Chang, Yu Jia; Wei, Po Li; Chang, Hui Wen; Chang, Chien Hsi; Huang, Ching Shui; Wu, Chih Hsiung; Ho, Yuan Soon.

In: Breast Cancer Research and Treatment, Vol. 129, No. 2, 09.2011, p. 331-345.

Research output: Contribution to journalArticle

@article{e151afbc70984221a6fbcd789c20e499,
title = "Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces α9-nicotinic acetylcholine receptor expression in human breast cancer cells",
abstract = "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.",
keywords = "AP1, Breast cancer, Estrogen, Estrogen receptor, Nicotine",
author = "Lee, {Chia Hwa} and Chang, {Ya Chieh} and Chen, {Ching Shyang} and Tu, {Shih Hsin} and Wang, {Ying Jan} and Chen, {Li Ching} and Chang, {Yu Jia} and Wei, {Po Li} and Chang, {Hui Wen} and Chang, {Chien Hsi} and Huang, {Ching Shui} and Wu, {Chih Hsiung} and Ho, {Yuan Soon}",
year = "2011",
month = "9",
doi = "10.1007/s10549-010-1209-0",
language = "English",
volume = "129",
pages = "331--345",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces α9-nicotinic acetylcholine receptor expression in human breast cancer cells

AU - Lee, Chia Hwa

AU - Chang, Ya Chieh

AU - Chen, Ching Shyang

AU - Tu, Shih Hsin

AU - Wang, Ying Jan

AU - Chen, Li Ching

AU - Chang, Yu Jia

AU - Wei, Po Li

AU - Chang, Hui Wen

AU - Chang, Chien Hsi

AU - Huang, Ching Shui

AU - Wu, Chih Hsiung

AU - Ho, Yuan Soon

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

KW - AP1

KW - Breast cancer

KW - Estrogen

KW - Estrogen receptor

KW - Nicotine

UR - http://www.scopus.com/inward/record.url?scp=80052616541&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052616541&partnerID=8YFLogxK

U2 - 10.1007/s10549-010-1209-0

DO - 10.1007/s10549-010-1209-0

M3 - Article

C2 - 20953833

AN - SCOPUS:80052616541

VL - 129

SP - 331

EP - 345

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 2

ER -