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G Protein Estrogen Receptor (GPER) Regulates Kv11.1 Ion Channel Activity in ERneg Breast Cancer Cells
Author(s) -
Gentile Saverio
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1048.8
Subject(s) - gper , breast cancer , cancer research , estrogen receptor , herg , cancer , cancer cell , potassium channel , receptor , estrogen , microbiology and biotechnology , biology , chemistry , medicine , endocrinology
Breast cancer is a major cause of death among women worldwide, and novel strategies need to be developed to lessen its morbidity. Although, the mechanism of breast cancer proliferation is poorly understood, it has been established that in cancer cells displaying an E2 receptor positive (ERpos) or E2 receptor negative (ERneg) phenotype, proliferation can be mediated by an E2‐dependent mechanism. Interestingly, recent studies have demonstrated that E2 effects on proliferation of ERneg breast cancer cells can be mediated by the G protein‐coupled receptor, GPER. However, very little is known about the biochemical signaling cascade activated by E2 via GPER. Clinical heterogeneity of breast cancers indicates new subsets of gene expression that can create novel molecular pathways mediating estrogen's (E2) effects on proliferation. The human ether‐a‐go‐go related gene (hERG) encodes the voltage‐gated potassium channel Kv11.1, which is primarily expressed in electrically excitable cells. Interestingly, recent translational research in cancer biology has revealed that Kv11.1 is robustly expressed in cancers of varying histogeneses, including breast cancer. Although, it is well established that Kv11.1 plays a major role in regulating membrane potential nothing is known about its role in breast cancer and its contribution in proliferation. Our experiments show that changes of Kv11.1 activity determine variation of proliferation rate in ERneg breast cancer cells. Electrophysiological, biochemical analyses show that Kv11.1 ion channel activity is stimulated by an E2‐activated signaling cascade via GPER in ERneg breast cancer cells. In addition, stimulation of Kv11.1 activity led to increase of intracellular calcium. Understanding the role of hormonal regulation of Kv11.1 ion channel will lead to discovery of a myriad of new potential drug target for cancer treatment.