SULT2B1B sulfotransferase: Induction by vitamin D receptor and reduced expression in prostate cancer

Young Kyo Seo, Nooshin Mirkheshti, Chung S. Song, Soyoung Kim, Sherry Dodds, Soon C. Ahn, Barbara Christy, Rosario Mendez-Meza, Michael M. Ittmann, Sherry Abboud-Werner, Bandana Chatterjee

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 prostateexpressed 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 freeDHEApool and, thus, conversion ofDHEAto androstenedione. Here wereport that in prostatectomy specimens from treatment-naive patients, SULT2B expression is markedly reduced in malignant tissue (P<.001, Mann-WhitneyU 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 levelmaypartly control prostate cancer growth, and its induction in a therapeutic setting may inhibit disease progression.

Original languageEnglish (US)
Pages (from-to)925-939
Number of pages15
JournalMolecular Endocrinology
Issue number6
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology


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