TY - JOUR
T1 - SULT2B1B sulfotransferase
T2 - Induction by vitamin D receptor and reduced expression in prostate cancer
AU - Seo, Young Kyo
AU - Mirkheshti, Nooshin
AU - Song, Chung S.
AU - Kim, Soyoung
AU - Dodds, Sherry
AU - Ahn, Soon C.
AU - Christy, Barbara
AU - Mendez-Meza, Rosario
AU - Ittmann, Michael M.
AU - Abboud-Werner, Sherry
AU - Chatterjee, Bandana
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84877890627&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877890627&partnerID=8YFLogxK
U2 - 10.1210/me.2012-1369
DO - 10.1210/me.2012-1369
M3 - Article
C2 - 23579488
AN - SCOPUS:84877890627
SN - 0888-8809
VL - 27
SP - 925
EP - 939
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 6
ER -