Nongenomic β estrogen receptors enhance β1 adrenergic signaling induced by the nicotine-derived carcinogen 4-(Methyinitrosamino)-1-(3-Pyridyl)-1-Butanone in human small airway epithelial cells

被引:41
作者
Majidi, Mourad
Al-Wadei, Hussein A.
Takahashi, Takashi
Schuller, Hildegard M.
机构
[1] Univ Tennessee, Coll Vet Med, Dept Pathobiol, Expt Oncol Lab, Knoxville, TN 37996 USA
[2] Nagoya Univ, Grad Sch Med, Ctr Neurol Dis & Canc, Div Mol Carcinogenesis, Nagoya, Aichi, Japan
关键词
D O I
10.1158/0008-5472.CAN-07-0483
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Women are at higher risk for the development of lung adenocarcinoma than men; however, the mechanisms responsible for this are poorly understood. in lung adenocarcinoma cells, the estrogen receptor beta (ER beta) is the predominating form. We found that 17 beta-estradiol enhanced proliferation of the putative cells of origin of lung adenocarcinoma, small airway epithelial cells (HPLD1), in response to the nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Reverse-phase protein microarrays combined with Western blotting revealed that NNK induced phosphorylation of ER beta, an effect that involved stimulation of the adrenergic receptors beta 1 (beta 1AR). In transiently transfected cells, beta 1AR coprecipitated with ER beta, which increased with NNK treatment. ER beta enhanced NNK-induced cyclic AMP accumulation as well as G alpha i-mediated mitogen-activated protein kinase/extracetlular signal-regulated kinase (ERK) 1/2 activation. Coexpression of beta 1AR and ER beta activated NNK-mediated ERK1/2 cooperatively. ER beta gene knockdown, as well as coexpression of the dominant negative Ras and Raf, reduced stimulation of ERK1/2 by NNK. Whereas NNK phosphorylated Akt at Thr(308) and Ser(473), ER beta had no effect on this activity. Luciferase reporter assays showed that, in response to NNK, ER6 stimulated transcription of serum responsive element (SRE) but had a very small effect on the activity of estrogen responsive element (ERE). Together, the phosphorylation of ER beta, the dependence on G alpha i proteins, the activation of ERK1/2, and the preferential targeting of SRE over the classic ERE pathway support a role for nongenomic ER beta in the development of smoking-associated lung cancer. This novel cooperation between beta 1AR and ER beta signaling may contribute to the prominence of lung adenocarcinoma in women.
引用
收藏
页码:6863 / 6871
页数:9
相关论文
共 50 条
[31]   Expression of estrogen receptors α and β in human lung tissue and cell lines [J].
Mollerup, S ;
Jorgensen, K ;
Berge, G ;
Haugen, A .
LUNG CANCER, 2002, 37 (02) :153-159
[32]  
Muscat JE, 1996, CANCER RES, V56, P5192
[33]   Expression, function, and clinical implications of the estrogen receptor β in human lung cancers [J].
Omoto, Y ;
Kobayashi, Y ;
Nishida, K ;
Tsuchiya, E ;
Eguchi, H ;
Nakagawa, K ;
Ishikawa, Y ;
Yamori, T ;
Iwase, H ;
Fujii, Y ;
Warner, M ;
Gustafsson, JÅ ;
Hayashi, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 285 (02) :340-347
[34]  
OREFFO VI, 1993, CARCINOGENESIS, V14, P4215
[35]   Regulation of postnatal lung development and homeostasis by estrogen receptor β [J].
Patrone, C ;
Cassel, TN ;
Pettersson, K ;
Piao, YS ;
Cheng, GJ ;
Ciana, P ;
Maggi, A ;
Warner, M ;
Gustafsson, JÅ ;
Nord, M .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (23) :8542-8552
[36]   Plasma membrane estrogen receptors signal to antiapoptosis in breast cancer [J].
Razandi, M ;
Pedram, A ;
Levin, ER .
MOLECULAR ENDOCRINOLOGY, 2000, 14 (09) :1434-1447
[37]  
Schuller HM, 1999, CANCER RES, V59, P4510
[38]   NNK-induced hamster lung adenocarcinomas over-express β2-adrenergic and EGFR signaling pathways [J].
Schuller, HM ;
Cekanova, M .
LUNG CANCER, 2005, 49 (01) :35-45
[39]   Tobacco-specific carcinogenic nitrosamines - Ligands for nicotinic acetylcholine receptors in human lung cancer cells [J].
Schuller, HM ;
Orloff, M .
BIOCHEMICAL PHARMACOLOGY, 1998, 55 (09) :1377-1384
[40]   Estrogen receptor pathways in lung cancer [J].
Stabile L.P. ;
Siegfried J.M. .
Current Oncology Reports, 2004, 6 (4) :259-267