Inactivation of GPR30 reduces growth of triple-negative breast cancer cells: possible application in targeted therapy

• DOI: 10.1007/s10549-012-1968-x
• Publication Date: 2012-01-30T10:02:42Z
• Authors: Rainer Girgert; Günter Emons; Carsten Gründker
• Keywords: Targeted Therapy; GPER; Triple-negative breast cancer; Cancer Therapy

Triple-negative breast cancers lack estrogen receptor α (ERα), progesterone receptor, and do not overexpress human epidermal growth factor 2 (Her-2). They are neither susceptible to endocrine therapy nor a using the anti-Her-2 antibody, trastuzumab. Therefore, an efficient targeted is warranted. tumors frequently express membrane bound G-protein coupled (GPR30). As proof of principle, we analyzed consequences knock-down GPR30 expression on regulation triple-negative cancer cell lines. Cells lines were transfected with siRNA against or control siRNA, was stimulated either 10(⁻⁹) M 17β-estradiol 10(⁻⁶) 4-hydroxytamoxifen. Cell proliferation measured Alamar blue staining. Activation c-Src (EGF)-receptor assessed western blot. Expression c-fos quantified by reverse transcription polymerase chain reaction. Seven days after transfection mRNA in MDA-MB-435 HCC1806 reduced 74 90%, respectively. 10(⁻⁸) enhanced 129.6±5.4% (p<0.05) 156.9±15.4% (p<0.05), 4-hydroxytamoxifen increased number 121.0±6.9% 124.5±12.1% (n.s.), This two estrogenic compounds completely prevented both In cells, activity Src kinase 3-fold estradiol 3.8-fold Transactivation EGF-receptor similarly Both 1.5- 3.1-fold, Knock-down abolished activation all these signaling pathways responsible for proliferation. A pharmacological inhibition specific small molecular inhibitors might prove be appropriate future.