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
N1 - Funding Information:
Acknowledgments This study was supported by the National Science Council [NSC 96-2628-B-038-003-MY3(1-3), NSC 98-2320-B-038-006-MY3(1-3)] and DOH99-TD-C-111-008 to Dr. Ho, and [NSC 97-2314-B-038-034-MY3(1-3)] to Dr. Wu, and by the Cathay Medical Center [96CGH-TMU-05 and 97CGH-TMU-02].
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.
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U2 - 10.1007/s10549-010-1209-0
DO - 10.1007/s10549-010-1209-0
M3 - Article
C2 - 20953833
AN - SCOPUS:80052616541
SN - 0167-6806
VL - 129
SP - 331
EP - 345
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -