PMID- 27341831
OWN - NLM
STAT- MEDLINE
DCOM- 20170927
LR  - 20240326
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Print)
IS  - 1541-7786 (Linking)
VI  - 14
IP  - 9
DP  - 2016 Sep
TI  - Cholesterol Sulfonation Enzyme, SULT2B1b, Modulates AR and Cell Growth Properties 
      in Prostate Cancer.
PG  - 776-86
LID - 10.1158/1541-7786.MCR-16-0137 [doi]
AB  - 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. IMPLICATIONS: 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. (c)2016 
      AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Vickman, Renee E
AU  - Vickman RE
AD  - Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue 
      University, West Lafayette, Indiana.
FAU - Crist, Scott A
AU  - Crist SA
AD  - Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue 
      University, West Lafayette, Indiana.
FAU - Kerian, Kevin
AU  - Kerian K
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana.
FAU - Eberlin, Livia
AU  - Eberlin L
AD  - Department of Chemistry, University of Texas at Austin, Austin, Texas.
FAU - Cooks, R Graham
AU  - Cooks RG
AD  - Department of Chemistry, Purdue University, West Lafayette, Indiana.
FAU - Burcham, Grant N
AU  - Burcham GN
AD  - Heeke Animal Disease Diagnostic Laboratory, Southern Indiana Purdue Agricultural 
      Center, Dubois, Indiana.
FAU - Buhman, Kimberly K
AU  - Buhman KK
AD  - Department of Nutrition Science, Purdue University, West Lafayette, Indiana.
FAU - Hu, Chang-Deng
AU  - Hu CD
AD  - Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 
      West Lafayette, Indiana.
FAU - Mesecar, Andrew D
AU  - Mesecar AD
AD  - Department of Biological Sciences, Purdue University, West Lafayette, Indiana.
FAU - Cheng, Liang
AU  - Cheng L
AD  - Department of Pathology, Indiana University School of Medicine, Indianapolis, 
      Indiana.
FAU - Ratliff, Timothy L
AU  - Ratliff TL
AD  - 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.
LA  - eng
GR  - P30 CA023168/CA/NCI NIH HHS/United States
GR  - R01 CA089062/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160624
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (AR protein, human)
RN  - 0 (Cholesterol Esters)
RN  - 0 (Receptors, Androgen)
RN  - EC 2.8.2.- (Sulfotransferases)
RN  - EC 2.8.2.2 (SULT2B1 protein, human)
RN  - KU576NT9O9 (cholesteryl sulfate)
SB  - IM
MH  - Cell Death/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/physiology
MH  - Cholesterol Esters/metabolism
MH  - Humans
MH  - Male
MH  - Prostatic Neoplasms/enzymology/genetics/*metabolism/*pathology
MH  - Receptors, Androgen/*metabolism
MH  - Sulfotransferases/*metabolism
PMC - PMC5111871
MID - NIHMS798253
COIS- There are no conflicts of interest to disclose by the authors of this manuscript.
EDAT- 2016/06/28 06:00
MHDA- 2017/09/28 06:00
PMCR- 2017/09/01
CRDT- 2016/06/26 06:00
PHST- 2016/04/21 00:00 [received]
PHST- 2016/06/11 00:00 [accepted]
PHST- 2016/06/26 06:00 [entrez]
PHST- 2016/06/28 06:00 [pubmed]
PHST- 2017/09/28 06:00 [medline]
PHST- 2017/09/01 00:00 [pmc-release]
AID - 1541-7786.MCR-16-0137 [pii]
AID - 10.1158/1541-7786.MCR-16-0137 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2016 Sep;14(9):776-86. doi: 10.1158/1541-7786.MCR-16-0137. Epub 
      2016 Jun 24.