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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2011

01-09-2011 | Preclinical study

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

Authors: 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

Published in: Breast Cancer Research and Treatment | Issue 2/2011

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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.
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Metadata
Title
Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces α9-nicotinic acetylcholine receptor expression in human breast cancer cells
Authors
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
Publication date
01-09-2011
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-1209-0

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