title: SULT2B1b sulfotransferase: induction by vitamin D receptor and reduced expression in prostate cancer.
abstract: An elevated tumor tissue androgen level, which reactivates androgen receptor in recurrent prostate cancer, arises from the intratumor synthesis of 5α-dihydrotestosterone through use of the precursor steroid dehydroepiandrosterone (DHEA) and is fueled by the steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD1), aldoketoreductase (AKR1C3), and steroid 5-alpha reductase, type 1 (SRD5A1) present in cancer tissue. Sulfotransferase 2B1b (SULT2B1b) (in short, SULT2B) is a prostate-expressed hydroxysteroid SULT that converts cholesterol, oxysterols, and DHEA to 3β-sulfates. DHEA metabolism involving sulfonation by SULT2B can potentially interfere with intraprostate androgen synthesis due to reduction of free DHEA pool and, thus, conversion of DHEA to androstenedione. Here we report that in prostatectomy specimens from treatment-naive patients, SULT2B expression is markedly reduced in malignant tissue (P < .001, Mann-Whitney U test) compared with robust expression in adjacent nonmalignant glands. SULT2B was detected in formalin-fixed specimens by immunohistochemistry on individual sections and tissue array. Immunoblotting of protein lysates of frozen cancer and matched benign tissue confirmed immunohistochemistry results. An in-house-developed rabbit polyclonal antibody against full-length human SULT2B was validated for specificity and used in the analyses. Ligand-activated vitamin D receptor induced the SULT2B1 promoter in vivo in mouse prostate and increased SULT2B mRNA and protein levels in vitro in prostate cancer cells. A vitamin D receptor/retinoid X receptor-α-bound DNA element (with a DR7 motif) mediated induction of the transfected SULT2B1 promoter in calcitriol-treated cells. SULT2B knockdown caused an increased proliferation rate of prostate cancer cells upon stimulation by DHEA. These results suggest that the tumor tissue SULT2B level may partly control prostate cancer growth, and its induction in a therapeutic setting may inhibit disease progression.
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA.
authors.forename: Young-Kyo
authors.initials: YK
authors.lastname: Seo
authors.forename: Nooshin
authors.initials: N
authors.lastname: Mirkheshti
authors.forename: Chung S
authors.initials: CS
authors.lastname: Song
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kim
authors.forename: Sherry
authors.initials: S
authors.lastname: Dodds
authors.forename: Soon C
authors.initials: SC
authors.lastname: Ahn
authors.forename: Barbara
authors.initials: B
authors.lastname: Christy
authors.forename: Rosario
authors.initials: R
authors.lastname: Mendez-Meza
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ittmann
authors.forename: Sherry
authors.initials: S
authors.lastname: Abboud-Werner
authors.forename: Bandana
authors.initials: B
authors.lastname: Chatterjee
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000918:Antibody Specificity; D001483:Base Sequence; D002117:Calcitriol / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018983:DNA Footprinting; D004790:Enzyme Induction; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011467:Prostate / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000502:physiology*; D020218:Response Elements; D017422:Sequence Analysis, DNA; D015238:Sulfotransferases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D000906:Antibodies; D018167:Receptors, Calcitriol; D015238:Sulfotransferases; C433248:SULT2B1 protein, human; D002117:Calcitriol