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Vitamin D Analogs in Cancer Prevention and Therapy pp 223–237Cite as

Vitamin D Autocrine System and Prostate Cancer

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Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 164))

Abstract

25-Hydroxyvitamin D-1α-hydroxylase (1α-OHase) is expressed in prostate cells.The expression suggests that local production of 1,25-dihydroxyvitamin D could provide an important cell growth regulatory mechanism. However,there is differential expression of 1α-OHase activity among the primary cultures of prostate cells derived from cancerous, benign prostatic hypertrophy and normal tissue, and among noncancerous (PZHPV-7) and various cancer cell lines (PC-3, DU145). No activity was found in cancer cell line LNCaP. The observed marked decrease in 1α-OHase activity in prostate cancer cells suggests some defect of the 1α-OHase in these cells. Using luciferase reporter gene assay,we observed a step-wise decrease in the basal promoter activity in two truncated promoter fragments, AN2 (_1,100 bp) and AN5 (-(-394 bp), with the highest basal activities found in PZHPV-7 and with loss of promoter activity in LNCaP. In order to understand the mechanism underlying the differential promoter activities among different prostate cells, we i0nvestigated the possible role of phosphorylation of cyclic AMP response element binding protein(CREB) on the regulation of 1α-OHase promoter activity in the four prostate cell lines. First we compared the levels of CREB phosphorylation among PZHPV-7, DU145, PC-3 and LNCaP cells by Western blot analysis using antibody against phosphorylated CREB. We observed that CREB was phosphorylated to a greater extent in PZHPV-7 than in DU145 cells.

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References

  • Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P(2000)Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 11:847–C852

    Article  Google Scholar 

  • Andrisani OM (1999) CREB-mediated transcriptional control. Crit Rev Eukaryot Gene Expr 9:19–C32

    Google Scholar 

  • Bikle DD, Nemanic MK, Whitney JO, Elias PW (1986) Neonatal human foreskin keratinocytes produce 1,25-dihydroxyvitamin D3. Biochemistry 25:1545–C1548

    Article  Google Scholar 

  • Brenza HL, Kimmel-Jehan C, Jehan F, Shinki T, Wakino S, Anazawa H, Suda T, DeLuca HF(1998) Parathyroid hormone activation of the 25-hydroxyvitamin D-1a-hydroxylase gene promoter. Proc Natl Acad Sci U S A 95:1387–C1391

    Article  Google Scholar 

  • Chen TC, Curthoys NP, Lagenaur CF, Puschett JB (1989) Characterization of primary cell cultures derived from rat renal proximal tubules. In Vitro 25:714–C722

    Google Scholar 

  • Chen TC, Persons K, Liu W-W, Chen ML, Holick MF (1995) The antiproliferative and differentiative activities of 1,25-dihydroxyvitamin D3 are potentiated by epidermal growth factor and attenuated by insulin in cultured human keratinocytes. J Invest Dermatol104:113–C117

    Google Scholar 

  • Chen TC, Young MV, Whitlatch LW, Zhu XH, Kong XF, Schwartz GG, Lokeshwar BL, Holick MF (1995) Expression and regulation of 25-hydroxyvitamin D3–1-alpha-hydroxylase incultured human prostatic cells. Bone 23 [Suppl 5]:S262

    Google Scholar 

  • Chen TC, Schwartz GG, Burnstein KL, Lokeshwar BL, Holick MF (2000a) The in vitro evaluationof 25-hydroxyvitamin D3 and 19-nor-1a,25-dihydroxyvitamin D2 for prostate cancer therapy. Clin Cancer Res 6:901–C908

    Google Scholar 

  • Chen TC, Whitlatch LW, Young MV, Flanagan JN, Schwartz GG, Lokeshwar BL, Kong XF, Xue P, Holick MF (2000b) Enhancement of 25-hydroxyvitamin D-1-alpha-hydroxylase activity in prostate cells by gene transfection: a novel approach for the treatment of prostate can-cer.Vitamin D endocrine system: structural, biological, genetic and clinical aspects. In:Norman AW, Bouillon R, Thomasset M (eds) Proceedings of the eleventh workshop on vitamin D, Nashville, TN, May 27-June 1, 2000, University of California, Riverside pp 525–C528

    Google Scholar 

  • Dusso A, Brown A, Slatopolsky E (1994) Extrarenal production of calcitriol. Semin Nephrol14:144–C155

    Google Scholar 

  • Fu GK, Lin D, Zhang MYH, Bikle DD, Shackleton CHL, Miller WL, Portale AA (1997) Cloning of human 25-hydroxyvitamin D-1a-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol 11:1961–C1970

    Article  Google Scholar 

  • Gross C, Stamey T, Hancock S, Feldman D (1998) Treatment of early recurrent prostate cancer with 1,25-Dihydroxyvitamin D3 (calcitriol). J Urol 159:2035–C2040

    Article  Google Scholar 

  • Holick MF (1995) Vitamin D: photobiology, metabolism, and clinical applications. In:DeGroot L, Besser H, Burger HG et al (eds), Endocrinology, 3rd edn. W.B. Saunders Philadelphia, pp 990–C1013

    Google Scholar 

  • Hsu JY, Feldman D, McNeal JE, Peehl DM (2001) Reduced 1a-hydroxylase activity in human prostate cancer cells correlates with decreased susceptibility to 25-hydroxyvitamin D3-induced growth inhibition. Cancer Res 61:2852–C2856

    Google Scholar 

  • Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–C1231

    Google Scholar 

  • Kong XF, Zhu XH, Pei YL, Jackson DM, Holick MF (1999) Molecular cloning, characterization,and promoter analysis of the human 25-hydroxhvitamin D3–1a-hydroxylase gene.Proc Natl Acad Sci U S A 96:6988–C6993

    Google Scholar 

  • Miller GJ, Stapleton GE, Ferrara JA, Lucia MS, Pfister S, Hedlund TE, Upadhya P (1992) The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1a,25-dihydroxyvitamin D3. Cancer Res 52:515–C520

    Google Scholar 

  • Miller WL,Portale AA (2000) Vitamin D 1a-hydroxylase. Trends Endocrinol Metab 11:315–C319

    Google Scholar 

  • Osborn JL,Schwartz GG, Bahnson R, Smith DC, Trump DL (1995) Phase II trial of oral 1,25-Dihydroxyvitamin D (calcitriol) in hormone refractory prostate cancer. Urol Oncol1:195–198

    PubMed  Google Scholar 

  • Peehl DM, Skowronski RJ, Leung GK, Wong ST, Stamey TA, Feldman D (1994) Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells.Cancer Res 54:805–C810

    Google Scholar 

  • Schwartz GG, Hulka BS (1990) Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis).Anticancer Res 10:1307–C1311

    Google Scholar 

  • Schwartz GG, Oeler TA, Uskokovic MR, Bahnson RR (1994) Human prostate cancer cell lines:inhibition of proliferation by vitamin D analogs. Anticancer Res 14:1077–C1081

    Google Scholar 

  • Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF (1998) Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxy vitamin D3. Cancer Epidemiol Biomark Prev 7:391–C395

    Google Scholar 

  • Shinki T, Shimada H, Wakino S, Anazawa, H, Hayashi M, Saruta T, Deluca HF, Suda T (1997)Cloning and expression of rat 25-hydroxyvitamin D3–1a-hydroxylase cDNA. Proc Natl Acad Sci U S A 94:12920–C12925

    Article  Google Scholar 

  • Skowronski RJ, Peehl DM, Feldman D (1993) Vitamin D and prostate cancer: 1,25-dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 132:1952–C1960

    Article  Google Scholar 

  • Skowronski RJ, Peehl DM, Feldman D (1995) Actions of vitamin D3 analogs on human prostate cancer cell lines: comparison with 1,25-dihydroxyvitamin D3. Endocrinology 136:20–C26

    Article  Google Scholar 

  • St-Arnaud R, Messerlian S, Moir JM, Omdahl JL, Glorieux FH (1997) The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J Bone Miner Res 12:1552–C1559

    Article  Google Scholar 

  • Takeyama KI,Kitanaka S,Sato T,Kobori M,Yanagisawa J, Kato S(1997)25-hydroxyvitamin D3 1a-hydroxylase and vitamin D synthesis. Science 277:1827–C1830

    Article  Google Scholar 

  • Whitlatch LW, Young MV, Schwartz GG, Flanagan JN, Burnstein KL,Lokeshwar BL, Rich ES,Holick MF, Chen TC (2002) 25-Hydroxyvitamin D-1a-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer. J Steroid Biochem MolBiol 81:135–C140

    Google Scholar 

  • Zhao XY, Ly LH, Holloway L, Feldman D (1999) Liarozole acts synergistically with 1,25-dihydroxyvitamin D3 to inhibit DU-145 human prostate cancer cell growth by blocking 24-hydroxylase activity. Endocrinology 140:2071–C2076

    Google Scholar 

  • Zhuang S-H, Burnstein KL (1998) Antiproliferative effect of 1a,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 139:1197–C1207

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, Endocrine Section, Boston University School of Medicine, 715 Albany Street, Boston, MA, 02118, USA

    Tai C. Chen

Authors
  1. Lilin Wang
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  2. Lyman W. Whitlatch
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  3. John N. Flanagan
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  4. Michael F. Holick
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  5. Tai C. Chen
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Editor information

Editors and Affiliations

  1. Hautklinik und Poliklinik der Universitätskliniken des Saarlandes, Kirrberger Str., 66421, Homburg/Saar

    Jörg Reichrath  & Wolfgang Tilgen  & 

  2. Frauenklinik des Universitätsklinikums der Eberhard-Karls-Universität, Calwerstr. 7, 71076, Tübingen

    Michael Friedrich

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© 2003 Springer-Verlag Berlin Heidelberg

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Wang, L., Whitlatch, L.W., Flanagan, J.N., Holick, M.F., Chen, T.C. (2003). Vitamin D Autocrine System and Prostate Cancer. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_16

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  • DOI: https://doi.org/10.1007/978-3-642-55580-0_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62435-3

  • Online ISBN: 978-3-642-55580-0

  • eBook Packages: Springer Book Archive

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