title: Glycogen synthase kinase-3: a potential preventive target for prostate cancer management.
abstract: OBJECTIVE
  Prostate cancers are the frequently diagnosed cancers in men, and patients with metastatic disease only have 28% chance for 5-year survival. Patients with low-risk tumors are subjected to active surveillance, whereas high-risk cases are actively treated. Unfortunately, there is no cure for patients with late-stage disease. Glycogen synthase kinase-3 (GSK-3, α and β) is a protein serine/threonine kinase and has diverse cellular functions and numerous substrates. We sought to summarize all the studies done with GSK-3 in prostate cancers and to provide a prospective direction for future work.
  
  
  METHODS
  A comprehensive search of the literature on the electronic databases PubMed was conducted for the subject terms of GSK-3 and prostate cancer. Gene mutation and expression information was extracted from Oncomine and COSMIC databases. Case reports were not included.
  
  
  RESULTS
  Accumulating evidence indicates that GSK-3α is mainly expressed in low-risk prostate cancers and is related to hormone-dependent androgen receptor (AR)-mediated gene expression, whereas GSK-3β is mainly expressed in high-risk prostate cancers and is related to hormone-independent AR-mediated gene expression. GSK-3 has been demonstrated as a positive regulator in AR transactivation and prostate cancer growth independent of the Wnt/β-catenin pathway. Different types of GSK-3inhibitors including lithium show promising results in suppressing tumor growth in different animal models of prostate cancer. Importantly, clinical use of lithium is associated with reduced cancer incidence in psychiatric patients.
  
  
  CONCLUSIONS
  Taken together, GSK-3 inhibition might be implicated in prostate cancer management as a preventive treatment.
authors.affiliation: Department of Urology, University of Kansas Medical Center, Kansas City, KS. Electronic address: bli@kumc.edu.
authors.forename: Benyi
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Urology, University of Kansas Medical Center, Kansas City, KS.
authors.forename: James Brantley
authors.initials: JB
authors.lastname: Thrasher
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS; Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS.
authors.forename: Paul
authors.initials: P
authors.lastname: Terranova
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D019468:Disease Management; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Cancer prevention and treatment; GSK-3; Lithium chloride; Prostate cancer; Small chemicals