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Re: Estrogen Receptor b Upregulates FOXO3a and Causes Induction of Apoptosis through PUMA in Prostate Cancer ˚ . Gustafsson € m and J. A P. Dey, A. Stro Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, and Department of BioSciences and Nutrition, Karolinska Institutet, Huddinge, Sweden Oncogene 2014; 33: 4213e4225.

Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.021 available at http://jurology.com/ Editorial Comment: This is the first known study to demonstrate that induction of FOXO3a expression has a role in its effect on apoptosis, besides the well-known post-translational modification of FOXO3a by phosphorylation. The authors identified 2 estrogen response element half-sites and an AP1 site downstream of the FOXO3a gene, and showed that this sequence up-regulates FOXO3a transcription. Furthermore, ERb-/- mice exhibited a strong decrease in expression of FOXO3a. In addition, the authors found ERb and FOXO3a to be co-expressed in benign prostatic hyperplasia but a strong reduction of both factors in higher grade prostate cancer. Because of the low number of cancer samples used in this study, the authors cannot conclude that high Gleason grade prostate cancer generally loses ERb expression. Other studies suggest that ERb may be involved in driving an aggressive prostate cancer phenotype. It is possible that the contradictory findings may depend on differences in function of ERb splice variants that are also knocked down by ERb siRNA and react with an N-terminal antibody. Further studies with a larger number of clinical samples will help to increase the understanding of the function of ERb in the prostate. Exploration of this newly discovered pathway connecting ERb to FOXO3a and PUMA might help in the development of new targeted drugs in the clinical management of prostate cancer. Anthony Atala, MD

Suggested Reading Hsu JL, Lee YJ, Leu WJ et al: Moniliformediquinone induces in vitro and in vivo antitumor activity through glutathione involved DNA damage response and mitochondrial stress in human hormone refractory prostate cancer. J Urol 2014; 191: 1429. Af H€allstr€om TM, Zhao H, Tian J et al: A tissue graft model of DNA damage response in the normal and malignant human prostate. J Urol 2014; 191: 842.

Re: Fructose-1,6-Bisphosphatase Opposes Renal Carcinoma Progression B. Li, B. Qiu, D. S. Lee, Z. E. Walton, J. D. Ochocki, L. K. Mathew, A. Mancuso, T. P. Gade, B. Keith, I. Nissim and M. C. Simon Abramson Family Cancer Research Institute and Departments of Cancer Biology, Radiology, Cell and Developmental Biology, and Pediatrics, Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Division of Child Development and Metabolic Disease, Children’s Hospital of Philadelphia and Howard Hughes Medical Institute, Philadelphia, Pennsylvania Nature 2014; 513: 251e255.

Abstract for this article http://dx.doi.org/10.1016/j.juro.2015.02.022 available at http://jurology.com/ Editorial Comment: Apart from von Hippel-Lindau loss, clear cell renal cell carcinomas exhibit a wide genetic heterogeneity. Recent large-scale analyses identified frequent mutations in 3 epigenetic genesdPBRM1, SETD2 and BAP1dall of which reside in a 43-megabase region on chromosome 3p that encompasses von Hippel-Lindau. Clear cell renal cell carcinoma is characterized histologically by the clear cell phenotype resulting from glycogen and lipid accumulation, suggesting that metabolic perturbations are a defining feature of these tumors. The authors demonstrate that the gluconeogenic enzyme FBP1 is ubiquitously depleted in clear cell renal cell carcinoma. FBP1 exhibits dual tumor suppressive functions mediated by 2 separate domains, explaining the universal loss of FBP1

Re: Estrogen receptor β upregulates FOXO3a and causes induction of apoptosis through PUMA in prostate cancer.

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