Expressions of genes encoding steroidogenic enzymes and their role in prostate carcinogenesis

Bartosz A. Frycz; Paweł P. Jagodziński

doi:10.20883/medical.e48

Authors

Bartosz A. Frycz Chair and Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland
Paweł P. Jagodziński Chair and Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland

DOI:

https://doi.org/10.20883/medical.e48

Keywords:

prostate cancer, steroidogenesis, steroidogenic enzymes, steroid hormone

Abstract

The concentration of sex steroid hormones in the prostate gland is controlled by their local synthesis and metabolism. These processes involve steroid metabolizing (steroidogenic) enzymes, which are necessary to produce the active form of androgens and estrogens at specific locations. Changes in gene expression of the steroid metabolizing enzymes may play an important role in prostate carcinogenesis by regulating sex steroid concentration in the prostate gland. The purpose of this review is to gather the most important reports connected with gene expression of the steroidogenic enzymes and to find correlations between gene expression and tumorigenesis in the prostate gland.

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References

Bethesda MD. Cancer Trends Progress Report – 2009/2010 Update, National Cancer Institute, NIH, DHHS. 2010 Aug. http://progressreport.cancer.gov

Wojciechowska U, Didkowska J, Zatoński W. Nowotwory złośliwe w Polsce w roku. 2006. Centrum Onkologii Instytut im. M. Skłodowskiej-Curie, Warszawa. 2008.

Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J et al. Human Prostate Cancer Risk Factors. Cancer. 2004 Nov;101(10):2371–490.

Soronen P, Laiti M, Törn S, Härkönen P, Patrikainen L, Li Y et al. Sex steroid hormone metabolism and prostate cancer. J Steroid Biochem Mol Biol. 2004 Nov;92(4):281–6.

Sharifi N. Minireview: Androgen metabolism in castration-resistant prostate cancer. Mol Endocrinol. 2013 May;27(5):708–14.

Hsing AW. Hormones and prostate cancer: what’s next? Epidemiol Rev. 2001;23(1):42–58.

Harkonen PL, Makel SI. Role of estrogens in development of prostate cancer. J Steroid Biochem Mol Biol. 2004 Nov;92(4):297–305.

Luu-The V. Analysis and characteristics of multiple types of human 17beta-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol. 2001 Jan-Mar;76(1–5):143–51.

Huggins C, Hodges CV. Studies of prostatic cancer: effect of castration, estrogen and androgen injections on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Jul;168(1):9–12.

Feldman BJ, Feldman D. The Development Of Androgen-Independent Prostate Cancer. Nat Rev Cancer. 2001 Oct;1(1):34–45.

Hovenian MS, Deming CL. The heterologous growth of cancer of the human prostate. Surg Gynecol Obstet. 1948 Jan;86(1):29–35.

Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003 Jul;349(3):215–224.

Noble RL. The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration. Cancer Res. 1977 Jun;37(6):1929–1933.

Lau KM, Leav I, Ho SM. Rat estrogen receptor-alpha and –beta and progesterone receptor mRNA expression in various prostatic lobes and microdissected normal and dysplastic epithelial tissues of the Noble rats. Endocrinology. 1998 Jan;139(1):424–7.

Harkonen PL, Makel SI. Role of estrogens in development of prostate cancer. J Steroid Biochem Mol Biol. 2004 Nov;92(4):297–305.

Nevalainen MT, Valve EM, Mäkelä SI, Bläuer M, Tuohimaa PJ, Härkönen PL. Estrogen and prolactin regulation of rat dorsal and lateral prostate in organ culture. Endocrinology. 1991 Aug;129(2):612–22.

Nevalainen MT, Härkönen PL, Valve EM, Ping W, Nurmi M, Martikainen PM. Hormone regulation of human prostate in organ culture. Cancer Res. 1993 Nov;53(21):5199–207.

Pylkkanen L, Santti R, Newbold R, McLachlan JA. Regional differences in the prostate of the neonatally estrogenized mouse. Prostate. 1991;18(2):117–29.

Friedman AE. The Estradiol-Dihydrotestosterone model of prostate cancer. Theor Biol Med Model. 2005 Mar;18;2:10.

Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008 Feb;100(3):170–83.

Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst. 1996 Aug;88(16):1118–26.

Labrie F, Luu-The V, Lin SX, Simard J, Labrie C. The Role of 17beta-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues. Trends Endocrinol Metab. 2000 Dec;11(10):421–7.

Nakamura Y, Miki Y, Suzuki T, Nakata T, Darnel AD, Moriya T et al. Steroid sulfatase and estrogen sulfotransferase in the atherosclerotic human aorta. Am J Pathol. 2003 Oct;163(4):1329–39.

Naitoh K, Honjo H, Yamamoto T, Urabe M, Ogino Y, Yasumura T, Nambara T. Estrone sulfatase and sulfotransferase activity in human breast cancer and endometrial cancer. J Steroid Biochem. 1989 Dec;33(6):1049–54.

Utsumi T, Yoshimura N, Takeuchi S, Maruta M, Maeda K, Harada N. Elevated steroid sulfatase expression in breast cancer. J Steroid Biochem Mol Biol. 2000 Jun;73(3–4):141–5.

Santner SJ, Feil PD, Santen RJ. In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. J Clin Endocrinol Metab. 1984 Jul;59(1):29–33.

Day JM, Tutill HJ, Foster PA, Bailey HV, Heaton WB, Sharland CM et al. Development of hormone-dependent prostate cancer models for the evaluation of inhibitors of 17beta-hydroxysteroid dehydrogenase type 3. Mol Cell Endocrinol. 2009 Mar;301(1–2):251–8.

Nakamura Y, Suzuki T, Fukuda T, Ito A, Endo M, Moriya T et al. Steroid Sulfatase and Estrogen Sulfotransferase in Human Prostate Cancer. Prostate. 2006 Jun;66(9):1005–12.

Simard J, Ricketts ML, Gingras S, Soucy P, Feltus FA, Melner MH. Molecular biology of the 3beta-hydroxysteroid dehydrogenase/ delta5-delta4 isomerase gene family. Endocr Rev. 2005 Jun;26(4):525–82.

Chang BL, Zheng SL, Hawkins GA, Isaacs SD, Wiley KE, Turner A et al. Joint Effect of HSD3B1 and HSD3B2 Genes Is Associated with Hereditary and Sporadic Prostate Cancer Susceptibility. Cancer Res. 2002 Mar;62(6):1784–9.

Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM et al. Increased Expression of Genes Converting Adrenal Androgens to Testosterone in Androgen-Independent Prostate Cancer. Cancer Res. 2006 Mar;66(5):2815–25.

Peltoketo H, Luu-The V, Simard J, Adamski J. 17beta-hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase (KSR) family; nomenclature and main characteristics of the17HSD/KSR enzymes. J Mol Endocrinol. 1999 Aug;23(1):1–11.

Adamski J, Jakob FJ. A guide to 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol. 2001 Jan;171 (1–2):1–4.

Koh E, Noda T, Kanaya J, Namiki M. Differential expression of 17beta-hydroxysteroid dehydrogenase isozyme genes in prostate cancer and noncancer tissues. Prostate. 2002 Oct;53(2):154–9.

Vihko P, Herrala A, Härkönen P, Isomaa V, Kaija H, Kurkela R. et al. Enzymes as modulators in malignant transformation. J Steroid Biochem Mol Biol. 2005 Feb;93 (2–5):277–83.

Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H et al. Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1- AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J. 2000 Oct;351(Pt 1):67–77.

Fung KM, Samara EN, Wong C, Metwalli A, Krlin R, Bane B et al. Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma. Endocrine-Endocr Relat Cancer. 2006 Mar;13(1):169–80.

Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM. Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells. Endocrinology. 2003 Jul;144(7):2922–32.

Lin HK, Jez JM, Schlegel BP, Peehl DM, Pachter JA, Penning TM. Expression and characterization of recombinant type 2 3alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3alpha/17beta-HSD activity and cellular distribution. Mol Endocrinol. 1997 Dec;11(13):1971–84.

Wang S, Yang Q, Fung KM, Lin HK. AKR1C2 and AKR1C3 mediated prostaglandin D2 metabolism augments the PI3K/Akt proliferative signaling pathway in human prostate cancer cells. Mol Cell Endocrinol. 2008 Jul;289 (1–2):60–6.

Dozmorov MG, Azzarello JT, Wren JD, Fung KM, Yang Q, Davis JS et al. Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progression. BMC Cancer. 2010 Dec;10:672.

Isaacs WB, Bova GS, Morton RA, Bussemakers MJ, Brooks JD, Ewing CM. Molecular biology of prostate cancer. Semin Oncol. 1994 Oct;21(5):514–21.

Jenkins EP, Hsieh CL, Milatovich A, Normington K, Berman DM, Francke U, Russell DW. Characterization and chromosomal mapping of a human steroid 5 alpha-reductase gene and pseudogene and mapping of the mouse homologue. Genomics. 1991 Dec;11(4):1102–12.

Brawley OW, Ford LG, Thompson I, Perlman JA, Kramer BS. 5alpha-reductase inhibition and prostate cancer prevention. Cancer Epidemiol Biomarkers Prev. 1994 Mar;3(2):177–82.

Makridakis NM, Ross RK, Pike MC, Crocitto LE, Kolonel LN, Pearce CL et al. Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA. Lancet. 1999 Sep;354(9183):975–8.

Kantoff PW, Febbo PG, Giovannucci E, Krithivas K, Dahl DM, Chang G et al. A polymorphism of the 5alpha-reductase gene and its association with prostate cancer: a case-control analysis. Cancer Epidemiol Biomarkers Prev. 1997 Mar;6(3):189–92.

Ross RK, Bernstein L, Lobo RA, Shimizu H, Stanczyk FZ, Pike MC, Henderson BE. 5alpha-Reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet. 1992 Apr;339(8798):887–9.

Ellem SJ, Schmitt JF, Pedersen JS, Frydenberg M, Risbridger GP. Local Aromatase Expression in Human Prostate Is Altered in Malignancy. J Clin Endocrinol Metab. 2004 May;89(5):2434–41.

Rohrmann S, Roberts WW, Walsh PC, Platz EA. Family history of prostate cancer and obesity in relation to high-grade disease and extraprostatic extension in young men with prostate cancer. Prostate. 2003 May;55(2):140–6.

Simpson ER, Mahendroo MS, Nichols JE, Bulun SE. Aromatase gene expression in adipose tissue: relationship to breast cancer. Int J Fertil Menopausal Stud. 1994;39 Suppl 2:75–83.

McPherson SJ, Wang H, Jones ME, Pedersen J, Iismaa TP, Wreford N et al. Elevated androgens and prolactin in aromatase-deficient mice cause enlargement, but not malignancy, of the prostate gland. Endocrinology. 2001 Jun;142(6):2458–67.

Modugno F, Weissfeld JL, Trump DL, Zmuda JM, Shea P, Cauley JA, Ferrell RE. Allelic Variants of Aromatase and the Androgen and Estrogen Receptors: Toward a Multigenic Model of Prostate Cancer Risk. Clin Cancer Res. 2001 Oct;7(10):3092–6.

Romero J, Garcia B, Campos F, Touijer KA. Prostate cancer biomarkers: Urol Oncol. 2014 Feb 1.

Stone NN, Stock RG, Unger P. Indications for seminal vesicle biopsy and laparoscopic pelvic lymph node dissection in men with localized carcinoma of the prostate. J Urol. 1995 Oct;154(4):1392–6.

Kar A, Scholz MC, Fegan JE, Crawford ED, Scardino PT, Kaldate RR, Brawer MK. Cell Cycle Progression (CCP) Score Significantly Modifies Treatment Decisions in Prostate Cancer: Results of an Ongoing Registry Trial ASCO Genitourinary Cancers Symposium, January 30 – February 1, 2014, San Francisco, CA. Poster Presentation.

Knezevic D, Goddard AD, Natraj N, Cherbavaz DB, Clark-Langone KM, Snable J et al. Analytical validation of the Oncotype DX Prostate Cancer Assay – A prognostic multi-gene RT-PCR test optimized for needle biopsies. 2013 SUO Annual Meeting – Rockville, MD. Poster Presentation.

Marks LS, Fradet Y, Deras IL, Blase A, Mathis J, Aubin SM et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology. 2007 Mar;69(3):532–5.

La Rosa FG, Jones C, Crawford ED, Van Neste L. Finding Occult Prostatic Cancer: The Value of Transperineal Mapping Biopsies and Epigenetic Assays. The Journal of OncoPathology, 2013.

Robinson K, Creed J, Reguly B, Powell C, Wittock R, Klein D et al. Accurate prediction of repeat prostate biopsy outcomes by a mitochondrial DNA deletion assay. Prostate Cancer Prostatic Dis. 2010 Jun;13(2):126–31.

Karantanos T, Corn PG, Thompson TC. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene. 2013 Dec;32(49):5501–11.

Vis AN, Schröder FH. Key targets of hormonal treatment of prostate cancer. Part 1: the androgen receptor and steroidogenic pathways. BJU Int. 2009 Aug;104(4):438–48.

Mohler JL, Gregory CW, Ford OH, Kim D, Weaver CM, Petrusz P et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004 Jan;10(2):440–8.

Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 2008 Aug;68(15):6407–15.

Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 2008 Jun;68(11):4447–54.

Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006 Mar;66(5):2815–25.

Berruti A, Pia A, Terzolo M. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 Aug;365(8):766.

Zelefsky MJ, Eastham JA, Sartor OA, Kantoff P. Cancer: Principles & Practice of Oncology (8th ed.). Philadelphia: Lippincott Williams & Wilkins. p. 1443.