The b2-adrenergic receptor and Her2 comprise a positive feedback loop in human breast cancer cells
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Ming Shi Dan Liu Huijun Duan Lu Qian Lina Wang Lijia Niu Huipeng Zhang Zheng Yong Zehui Gong Lun Song Ming Yu Meiru Hu Qing Xi
- چاپ و سال / کشور: 2010
Description
In this study, b2-AR level was found to be up-regulated in MCF-7 cells overexpressing Her2 (MCF-7/ Her2). Correlation of b2-AR level with Her2 status was demonstrated in breast cancer tissue samples. Constitutive phosphorylation of ERK, mRNA expression up-regulation of catecholamine-synthesis enzymes, and increased epinephrine release were detected in MCF-7/Her2 cells. b2-AR expression induced by epinephrine and involvement of ERK signaling were validated. The data indicate that Her2 overexpression and excessive phosphorylation of ERK cause epinephrine autocrine release from breast cancer cells, resulting in up-regulation of b2-AR expression. The data also showed that catecholamine prominently stimulated Her2 mRNA expression and promoter activity. The activation and nuclear translocation of STAT3 triggered by isoproterenol were observed. Enhanced binding activities of STAT3 to the Her2 promoter after isoproterenol stimulation were verified. Using STAT3 shRNA and dominant negative STAT3 mutant, the role of STAT3 in isoproterenol-induced Her2 expression was further confirmed. The data support a model where b2-AR and Her2 comprise a positive feedback loop in human breast cancer cells.
Breast Cancer Res Treat (2011) 125:351–362 Received: 19 January 2010 / Accepted: 24 February 2010 / Published online: 17 March 2010 Springer Science+Business Media, LLC. 2010
