title: Cholesterol Sulfonation Enzyme, SULT2B1b, Modulates AR and Cell Growth Properties in Prostate Cancer.
abstract: Cholesterol accumulates in prostate lesions and has been linked to prostate cancer incidence and progression. However, how accumulated cholesterol contributes to prostate cancer development and progression is not completely understood. Cholesterol sulfate (CS), the primary sulfonation product of cholesterol sulfotransferase (SULT2B1b), accumulates in human prostate adenocarcinoma and precancerous prostatic intraepithelial neoplasia (PIN) lesions compared with normal regions of the same tissue sample. Given the enhanced accumulation of CS in these lesions, it was hypothesized that SULT2B1b-mediated production of CS provides a growth advantage to these cells. To address this, prostate cancer cells with RNAi-mediated knockdown (KD) of SULT2B1b were used to assess the impact on cell growth and survival. SULT2B1b is expressed and functional in a variety of prostate cells, and the data demonstrate that SULT2B1b KD, in LNCaP and other androgen-responsive (VCaP and C4-2) cells, results in decreased cell growth/viability and induces cell death. SULT2B1b KD also decreases androgen receptor (AR) activity and expression at mRNA and protein levels. While AR overexpression has no impact on SULT2B1b KD-mediated cell death, the addition of exogenous androgen is able to partially rescue the growth inhibition induced by SULT2B1b KD in LNCaP cells. These results suggest that SULT2B1b positively regulates the AR either through alterations in ligand availability or by interaction with critical coregulators that influence AR activity.
  
  
  
  These findings provide evidence that SULT2B1b is a novel regulator of AR activity and cell growth in prostate cancer and should be further investigated for therapeutic potential. Mol Cancer Res; 14(9); 776-86. ©2016 AACR.
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana.
authors.forename: Renee E
authors.initials: RE
authors.lastname: Vickman
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Crist
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kerian
authors.affiliation: Department of Chemistry, University of Texas at Austin, Austin, Texas.
authors.forename: Livia
authors.initials: L
authors.lastname: Eberlin
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Cooks
authors.affiliation: Heeke Animal Disease Diagnostic Laboratory, Southern Indiana Purdue Agricultural Center, Dubois, Indiana.
authors.forename: Grant N
authors.initials: GN
authors.lastname: Burcham
authors.affiliation: Department of Nutrition Science, Purdue University, West Lafayette, Indiana.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Buhman
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana.
authors.forename: Chang-Deng
authors.initials: CD
authors.lastname: Hu
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mesecar
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana. Purdue University Center for Cancer Research, West Lafayette, Indiana. tlratliff@purdue.edu.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Ratliff
mesh_terms: D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D002788:Cholesterol Esters; D011944:Receptors, Androgen; D015238:Sulfotransferases; C433248:SULT2B1 protein, human; C007045:cholesteryl sulfate