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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our data revealed the potential dual roles of E2 in regulating RCC growth via autophagy and apoptosis pathways.
Graduate Institute of Nutrition and Food Sciences, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan, R.O.C. Graduate Institute of Basic Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan, R.O.C. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan, R.O.C. Department of Surgery, Cathay General Hospital, Taipei, Taiwan, R.O.C.
Kuo-Chiang
KC
Chen
Department of Surgery, Cathay General Hospital, Taipei, Taiwan, R.O.C.
Chih-Ming
CM
Lin
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan, R.O.C. Department of Medical Research, Cathay General Hospital, Taipei, Taiwan, R.O.C. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Chi-Jung
CJ
Huang
Department of Surgery, Sijhih Cathay General Hospital, New Taipei, Taiwan, R.O.C.
Shao-Kuan
SK
Chen
Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Sheng-Tang
ST
Wu
Graduate Institute of Basic Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan, R.O.C. Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C. 089052@mail.fju.edu.tw 053824@mail.fju.edu.tw.
Han-Sun
HS
Chiang
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan, R.O.C. 089052@mail.fju.edu.tw 053824@mail.fju.edu.tw.
Wei-Chi
WC
Ku
D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D011960:Receptors, Estrogen / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D011960:Receptors, Estrogen; D004958:Estradiol
17-β-estradiol; apoptosis; autophagy; estrogen receptor; quantitative phosphoproteomics; renal cell carcinoma