Dual Roles of 17-β Estradiol in Estrogen Receptor-dependent Growth Inhibition in Renal Cell Carcinoma

• Published in: Cancer genomics & proteomics Vol. 13; no. 3; p. 219
• Main Authors: Chen, Kuo-Chiang, Lin, Chih-Ming, Huang, Chi-Jung, Chen, Shao-Kuan, Wu, Sheng-Tang, Chiang, Han-Sun, Ku, Wei-Chi
• Format: Journal Article
• Language: English
• Published: Greece 01.05.2016
• Subjects: Apoptosis - drug effects; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Chromatography, Liquid; Estradiol - metabolism; Estradiol - pharmacology; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Metabolome; Metabolomics - methods; Receptors, Estrogen - metabolism; Tandem Mass Spectrometry; apoptosis; renal cell carcinoma; autophagy; 17-β-estradiol; estrogen receptor; quantitative phosphoproteomics
• ISSN: 1790-6245

It has been proposed that 17-β-estradiol (E2) activates estrogen receptor and inhibits renal cell carcinoma (RCC) growth. In the present study we explored the role of E2 and ER in the regulation of RCC growth. The RCC cell line ACHN was treated by E2 combining with E2 antagonist Fulvestrant or ER knockdown, and cell growth was monitored. Quantitative phosphoproteomics was applied to study the E2 regulated non-genomic phosphorylation changes. Western blotting, immunofluorescence microscopy, and apoptosis assays were used for validation. E2 induced ER-dependent growth inhibition in RCC cell lines. Quantitative phosphoproteomics revealed that E2 induced both apoptosis and autophagy. Cellular apoptosis was confirmed by altered mitochondrial membrane potential, and ER-dependent autophagosome formation was also found. Our data revealed the potential dual roles of E2 in regulating RCC growth via autophagy and apoptosis pathways.