A novel polymorphism in a Forkhead Box A1 (FOXA1) binding site of the human UDP glucuronosyltransferase 2B17 gene modulates promoter activity and is associated with altered levels of circulating androstane-3α,17β-diol glucuronide

Molecular Pharmacology

Volumn 78, Issue 4, 2010, Pages 714-722

  Hu, Dong Gui ^a   Gardner Stephen, Dione ^a   Severi, Gianluca ^b,c   Gregory, Philip A ^d,e   Treloar, Joanna ^f   Giles, Graham G ^b,c   English, Dallas R ^b,c   Hopper, John L ^c   Tilley, Wayne D ^f   Mackenzie, Peter I ^a  

^a FLINDERS UNIVERSITY   (Australia)

^b CANCER EPIDEMIOLOGY CENTRE   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d CENTRE FOR CANCER BIOLOGY   (Australia)

^e UNIVERSITY OF ADELAIDE   (Australia)

^f UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROSTANEDIOL; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 2B17; HEPATOCYTE NUCLEAR FACTOR 3ALPHA; UNCLASSIFIED DRUG; ANDROSTANE-3,17-DIOL GLUCURONIDE; FOXA1 PROTEIN, HUMAN; UGT2B17 PROTEIN, HUMAN;

AGED; ALLELE; ARTICLE; BINDING SITE; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION; HUMAN; MALE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROMOTER REGION; SINGLE NUCLEOTIDE POLYMORPHISM; ANALOGS AND DERIVATIVES; BLOOD; COMPARATIVE STUDY; GENETIC POLYMORPHISM; GENETICS; METABOLISM; PHYSIOLOGY; PROSTATE TUMOR; TUMOR CELL LINE;

ANDROSTANE-3,17-DIOL; BINDING SITES; CELL LINE, TUMOR; GLUCURONOSYLTRANSFERASE; HEPATOCYTE NUCLEAR FACTOR 3-ALPHA; HUMANS; MALE; POLYMORPHISM, GENETIC; PROMOTER REGIONS, GENETIC; PROSTATIC NEOPLASMS;

EID: 77957235306     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.110.065953     Document Type: Article

References (38)

1. Bao BY, Chuang BF, Wang Q, Sartor O, Balk SP, Brown M, Kantoff PW, and Lee GS (2008) Androgen receptor mediates the expression of UDP- glucuronosyltransferase 2 B15 and B17 genes. Prostate 68:839-848. (Pubitemid 351845215)
2. Barbier O, Lapointe H, El Alfy M, Hum DW, and Bélanger A (2000) Cellular localization of uridine diphosphoglucuronosyltransferase 2B enzymes in the human prostate by in situ hybridization and immunohistochemistry. J Clin Endocrinol Metab 85:4819-4826. (Pubitemid 32157673)
3. Beaulieu M, Lévesque E, Tchernof A, Beatty BG, Bélanger A, and Hum DW (1997) Chromosomal localization, structure, and regulation of the UGT2B17 gene, encoding a C19 steroid metabolizing enzyme. DNA Cell Biol 16:1143-1154. (Pubitemid 27479382)
4. Bélanger A, Pelletier G, Labrie F, Barbier O, and Chouinard S (2003) Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends Endocrinol Metab 14:473-479. (Pubitemid 37517349)
5. Bowers LD (2008) Testosterone doping: dealing with genetic differences in metabolism and excretion. J Clin Endocrinol Metab 93:2469-2471.
6. Chouinard S, Pelletier G, Bélanger A, and Barbier O (2004) Cellular specific expression of the androgen-conjugating enzymes UGT2B15 and UGT2B17 in the human prostate epithelium. Endocr Res 30:717-725. (Pubitemid 40070159)
7. Chouinard S, Pelletier G, Bélanger A, and Barbier O (2006) Isoform-specific regulation of uridine diphosphate-glucuronosyltransferase 2B enzymes in the human prostate: differential consequences for androgen and bioactive lipid inactivation. Endocrinology 147:5431-5442. (Pubitemid 44790598)
8. Congiu M, Mashford ML, Slavin JL, and Desmond PV (2002) UDP glucuronosyltransferase mRNA levels in human liver disease. Drug Metab Dispos 30:129-134. (Pubitemid 34106530)
9. Gallagher CJ, Kadlubar FF, Muscat JE, Ambrosone CB, Lang NP, and Lazarus P (2007) The UGT2B17 gene deletion polymorphism and risk of prostate cancer. A case-control study in Caucasians. Cancer Detect Prev 31:310-315.
10. Gao N, Zhang J, Rao MA, Case TC, Mirosevich J, Wang Y, Jin R, Gupta A, Rennie PS, and Matusik RJ (2003) The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and androgen receptor in transcriptional regulation of prostatic genes. Mol Endocrinol 17:1484-1507. (Pubitemid 36930465)
11. Gardner-Stephen DA, Gregory PA, and Mackenzie PI (2005) Identification and characterization of functional hepatocyte nuclear factor 1-binding sites in UDP-glucuronosyltransferase genes. Methods Enzymol 400:22-46.
12. Giles GG, Severi G, McCredie MR, English DR, Johnson W, Hopper JL, and Boyle P (2001) Smoking and prostate cancer: findings from an Australian case-control study. Ann Oncol 12:761-765. (Pubitemid 32655083)
13. Gregory PA, Hansen AJ, and Mackenzie PI (2000) Tissue specific differences in the regulation of the UDP glucuronosyltransferase 2B17 gene promoter. Pharmacogenetics 10:809-820.
14. Gregory PA and Mackenzie PI (2002) The homeodomain Pbx2-Prep1 complex modulates hepatocyte nuclear factor 1alpha-mediated activation of the UDP-glucuronosyltransferase 2B17 gene. Mol Pharmacol 62:154-161.
15. Hayes VM, Severi G, Padilla EJ, Morris HA, Tilley WD, Southey MC, English DR, Sutherland RL, Hopper JL, Boyle P, et al. (2007) 5alpha-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia. Int J Cancer 120:776-780. (Pubitemid 46175396)
16. Hu DG and Mackenzie PI (2009) Estrogen receptor alpha, fos-related antigen-2, and c-Jun coordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17beta-estradiol in MCF-7 cells. Mol Pharmacol 76:425-439.
17. Jakobsson J, Ekström L, Inotsume N, Garle M, Lorentzon M, Ohlsson C, Roh HK, Carlström K, and Rane A (2006) Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. J Clin Endocrinol Metab 91:687-693. (Pubitemid 43236944)
18. Juul A, Sørensen K, Aksglaede L, Garn I, Rajpert-De Meyts E, Hullstein I, Hemmersbach P, and Ottesen AM (2009) A common deletion in the uridine diphosphate glucuronyltransferase (UGT) 2B17 gene is a strong determinant of androgen excretion in healthy pubertal boys. J Clin Endocrinol Metab 94:1005-1011.
19. Kaeding J, Bélanger J, Caron P, Verreault M, Bélanger A, and Barbier O (2008a) Calcitrol (1alpha,25-dihydroxyvitamin D3) inhibits androgen glucuronidation in prostate cancer cells. Mol Cancer Ther 7:380-390. (Pubitemid 351302531)
20. Kaeding J, Bouchaert E, Bélanger J, Caron P, Chouinard S, Verreault M, Larouche O, Pelletier G, Staels B, Bélanger A, et al. (2008b) Activators of the farnesoid X receptor negatively regulate androgen glucuronidation in human prostate cancer LNCAP cells. Biochem J 410:245-253. (Pubitemid 351346182)
21. Karypidis AH, Olsson M, Andersson SO, Rane A, and Ekström L (2008) Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate. Pharmacogenomics J 8:147-151.
22. Lévesque E, Beaulieu M, Guillemette C, Hum DW, and Bélanger A (1998) Effect of interleukins on UGT2B15 and UGT2B17 steroid uridine diphosphate-glucuronosyltransferase expression and activity in the LNCaP cell line. Endocrinology 139:2375-2381.
23. Lupien M, Eeckhoute J, Meyer CA, Wang Q, Zhang Y, Li W, Carroll JS, Liu XS, and Brown M (2008) FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132:958-970.
24. Mackenzie PI, Bock KW, Burchell B, Guillemette C, Ikushiro S, Iyanagi T, Miners JO, Owens IS, and Nebert DW (2005) Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics 15:677-685.
25. Mirosevich J, Gao N, Gupta A, Shappell SB, Jove R, and Matusik RJ (2006) Expression and role of Foxa proteins in prostate cancer. Prostate 66:1013-1028.
26. Murata M, Warren EH, and Riddell SR (2003) A human minor histocompatibility antigen resulting from differential expression due to a gene deletion. J Exp Med 197:1279-1289.
27. Myatt SS and Lam EW (2007) The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 7:847-859.
28. Olsson M, Lindström S, Häggkvist B, Adami HO, Bälter K, Stattin P, Ask B, Rane A, Ekström L, and Grönberg H (2008) The UGT2B17 gene deletion is not associated with prostate cancer risk. Prostate 68:571-575.
29. Park J, Chen L, Ratnashinge L, Sellers TA, Tanner JP, Lee JH, Dossett N, Lang N, Kadlubar FF, Ambrosone CB, et al. (2006) Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men. Cancer Epidemiol Biomarkers Prev 15:1473-1478.
30. Park JY, Tanner JP, Sellers TA, Huang Y, Stevens CK, Dossett N, Shankar RA, Zachariah B, Heysek R, and Pow-Sang J (2007) Association between polymorphisms in HSD3B1 and UGT2B17 and prostate cancer risk. Urology 70:374-379.
31. Schulze JJ, Lundmark J, Garle M, Skilving I, Ekström L, and Rane A (2008) Doping test results dependent on genotype of uridine diphospho- glucuronosyl transferase 2B17, the major enzyme for testosterone glucuronidation. J Clin Endocrinol Metab 93:2500-2506.
32. Severi G, Giles GG, Southey MC, Tesoriero A, Tilley W, Neufing P, Morris H, English DR, McCredie MR, Boyle P, et al. (2003) ELAC2/HPC2 polymorphisms, prostate-specific antigen levels, and prostate cancer. J Natl Cancer Inst 95:818-824. (Pubitemid 36798429)
33. Severi G, Morris HA, MacInnis RJ, English DR, Tilley W, Hopper JL, Boyle P, and Giles GG (2006) Circulating steroid hormones and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 15:86-91.
34. Swanson C, Mellström D, Lorentzon M, Vandenput L, Jakobsson J, Rane A, Karlsson M, Ljunggren O, Smith U, Eriksson AL, et al. (2007) The uridine diphosphate glucuronosyltransferase 2B15 D85Y and 2B17 deletion polymorphisms predict the glucuronidation pattern of androgens and fat mass in men. J Clin Endocrinol Metab 92:4878-4882.
35. Turgeon D, Carrier JS, Lévesque E, Hum DW, and Bélanger A (2001) Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members. Endocrinology 142:778-787.
36. Wang Q, Li W, Liu XS, Carroll JS, Jänne OA, Keeton EK, Chinnaiyan AM, Pienta KJ, and Brown M (2007) A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol Cell 27:380-392.
37. Wilson W 3rd, Pardo-Manuel de Villena F, Lyn-Cook BD, Chatterjee PK, Bell TA, Detwiler DA, Gilmore RC, Valladeras IC, Wright CC, Threadgill DW, et al. (2004) Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics 84:707-714.
38. Yang TL, Chen XD, Guo Y, Lei SF, Wang JT, Zhou Q, Pan F, Chen Y, Zhang ZX, Dong SS, et al. (2008) Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis. Am J Hum Genet 83:663-674.