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Calcitriol induces transcription of the placental transforming growth factor β gene in prostate cancer cells via an androgen-independent mechanism

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Abstract

Calcitriol (1α,25-dihydroxycholecalciferol) suppresses the growth of prostate cancer cells. Growth suppression of hormone-sensitive LNCaP prostate cancer cells by calcitriol is believed to depend on androgens, but the mechanisms of the interactions between the calcitriol-and androgen-dependent signaling pathways is unclear. A previous search for calcitriol-responsive genes in LNCaP cells with cDNA microarrays has shown that calcitriol regulates the expression of the gene for the placental transforming growth factor β (PTGF-β), which suppresses prostate cancer cell proliferation. A study was made of whether expression of the PTGF-β gene is regulated by 5α-dihydrotestosterone and whether induction of this gene by calcitriol is androgen-dependent. Quantitative PCR showed that 5α-dihydrotestosterone increases the level of the PTGF-β mRNA. Neither 5α-dihydrotestosterone nor the antiandrogen Casodex affected the calcitriol-induced level of the PTGF-β mRNA. It was assumed that calcitriol stimulates production of PTGF-β independently of 5α-dihydrotestosterone and that its effect on prostate cancer cell growth is partly mediated by an androgen-independent mechanism.

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References

  1. Miller G.J., Stapleton G.E., Ferrara J.A., Lucia M.S., Pfister S., Hedlund T.E., Upadhya P. 1992. The human prostatic carcinoma cell line LNCaP expresses biologically active, specific receptors for 1alpha,25-dihydroxyvitamin D3. Cancer Res. 52, 515–520.

    CAS  PubMed  Google Scholar 

  2. Hsieh T., Wu J.M. 1997. Induction of apoptosis and altered nuclear/cytoplasmic distribution of the androgen receptor and prostate-specific antigen by 1alpha,25-dihydroxyvitamin D3 in androgen-responsive LNCaP cells. Biochem. Biophys. Res. Commun. 235, 539–544.

    Article  CAS  PubMed  Google Scholar 

  3. Zhuang S.H., Burnstein K.L. 1998. Antiproliferative effect of 1alpha,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology. 139, 1197–1207.

    Article  CAS  PubMed  Google Scholar 

  4. Miller G.J., Stapleton G.E., Hedlund T.E., Moffat K.A. 1995. Vitamin D receptor expression, 24-hydroxylase activity, and inhibition of growth by 1 alpha,25-dihydroxyvitamin D3 in seven human prostatic carcinoma cell lines. Clin. Cancer Res. 1, 997–1003.

    CAS  PubMed  Google Scholar 

  5. Horoszewicz J.S., Leong S.S., Kawinski E., Karr J.P., Rosenthal H., Chu T.M., Mirand E.A., Murphy G.P. 1983. LNCaP model of human prostatic carcinoma. Cancer Res. 43, 1809–1818.

    CAS  PubMed  Google Scholar 

  6. Zhao X.Y., Ly L.H., Peehl D.M., Feldman D. 1997. 1alpha,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are androgen-dependent. Endocrinology. 138, 3290–3298.

    Article  CAS  PubMed  Google Scholar 

  7. Qiao S., Pennanen P., Nazarova N., Lou Y.R., Tuohimaa P. 2003. Inhibition of fatty acid synthase expression by 1alpha,25-dihydroxyvitamin D3 in prostate cancer cells. J. Steroid Biochem. Mol. Biol. 85, 1–8.

    Article  CAS  PubMed  Google Scholar 

  8. Zhao X.Y., Peehl D.M., Navone N.M., Feldman D. 2000. 1alpha,25-dihydroxyvitamin D3 inhibits prostate cancer cell growth by androgen-dependent and androgen-independent mechanisms. Endocrinology. 141, 2548–2556.

    CAS  PubMed  Google Scholar 

  9. Ahonen M.H., Zhuang Y.H., Aine R., Ylikomi T., Tuohimaa P. 2000. Androgen receptor and vitamin D receptor in human ovarian cancer: Growth stimulation and inhibition by ligands. Int. J. Cancer. 86, 40–46.

    Article  CAS  PubMed  Google Scholar 

  10. Escaleira M.T., Sonohara S., Brentani M.M. 1993. Sex steroids induced up-regulation of 1.25-(OH)2 vitamin D3 receptors in T 47D breast cancer cells. J. Steroid Biochem. Mol. Biol. 45, 257–263.

    Article  CAS  PubMed  Google Scholar 

  11. Nazarova N., Qiao S., Golovko O., Lou Y.R., Tuohimaa P. 2004. Calcitriol-induced prostate-derived factor: Autocrine control of prostate cancer cell growth. Int. J. Cancer. 112, 951–958.

    Article  CAS  PubMed  Google Scholar 

  12. Paralkar V.M., Vail A.L., Grasser W.A., Brown T.A., Xu H., Vukicevic S., Ke H.Z., Qi H., Owen T.A., Thompson D.D. 1998. Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family. J. Biol. Chem. 273, 13760–13767.

    Article  CAS  PubMed  Google Scholar 

  13. Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L. 1997. PLAB, a novel placental bone morphogenetic protein. Biochim. Biophys. Acta. 1354, 40–44.

    CAS  PubMed  Google Scholar 

  14. Bootcov M.R., Bauskin A.R., Valenzuela S.M., Moore A.G., Bansal M., He X.Y., Zhang H.P., Donnellan M., Mahler S., Pryor K., Walsh B.J., Nicholson R.C., Fairlie W.D., Por S.B., Robbins J.M., Breit S.N. 1997. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc. Natl. Acad. Sci. USA. 94, 11514–11519.

    Article  CAS  PubMed  Google Scholar 

  15. Bottner M., Suter-Crazzolara C., Schober A., Unsicker K. 1999. Expression of a novel member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues. Cell Tissue Res. 297, 103–110.

    CAS  PubMed  Google Scholar 

  16. Strelau J., Bottner M., Lingor P., Suter-Crazzolara C., Galter D., Jaszai J., Sullivan A., Schober A., Krieglstein K., Unsicker K. 2000. GDF-15/MIC-1 a novel member of the TGF-beta superfamily. J. Neural Transm. Suppl. 60, 273–276.

    PubMed  Google Scholar 

  17. Baek S.J., Horowitz J.M., Eling T.E. 2001. Molecular cloning and characterization of human nonsteroidal anti-inflammatory drug-activated gene promoter. Basal transcription is mediated by Sp1 and Sp3. J. Biol. Chem. 276, 33384–33392.

    CAS  PubMed  Google Scholar 

  18. Krishnan A.V., Peehl D.M., Feldman D. 2003. Inhibition of prostate cancer growth by vitamin D: Regulation of target gene expression. J. Cell. Biochem. 88, 363–371.

    Article  CAS  PubMed  Google Scholar 

  19. Li P.X., Wong J., Ayed A., Ngo D., Brade A.M., Arrowsmith C., Austin R.C., Klamut H.J. 2000. Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression. J. Biol. Chem. 275, 20127–20135.

    CAS  PubMed  Google Scholar 

  20. Tan M., Wang Y., Guan K., Sun Y. 2000. PTGF-beta, a type beta transforming growth factor (TGF-beta) superfamily member, is a p53 target gene that inhibits tumor cell growth via TGF-beta signaling pathway. Proc. Natl. Acad. Sci. USA. 97, 109–114.

    CAS  PubMed  Google Scholar 

  21. Baek S.J., Kim K.S., Nixon J.B., Wilson L.C., Eling T.E. 2001. Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol. Pharmacol. 59, 901–908.

    CAS  PubMed  Google Scholar 

  22. Liu T., Bauskin A.R., Zaunders J., Brown D.A., Pankhurst S., Russell P.J., Breit S.N. 2003. Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res. 63, 5034–5040.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, St. Petersburg State University, St. Petersburg, 119034, Russia

    N. Yu. Nazarova & G. I. Chikhirzhina

  2. Department of Anatomy, Medical School, University of Tampere, Tampere, 33104, Finland

    N. Yu. Nazarova & P. Tuohimaa

  3. Drug Discovery Graduate School, University of Turku, Turku, 20520, Finland

    N. Yu. Nazarova

  4. Department of Clinical Chemistry, Tampere University Hospital, Tampere, 33014, Finland

    P. Tuohimaa

Authors
  1. N. Yu. Nazarova
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  2. G. I. Chikhirzhina
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  3. P. Tuohimaa
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Additional information

Original Russian Text © N.Yu. Nazarova, G.I. Chikhirzhina, P. Tuohimaa, 2006, published in Molekulyarnaya Biologiya, 2006, Vol. 40, No. 1, pp. 84–89.

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Nazarova, N.Y., Chikhirzhina, G.I. & Tuohimaa, P. Calcitriol induces transcription of the placental transforming growth factor β gene in prostate cancer cells via an androgen-independent mechanism. Mol Biol 40, 72–76 (2006). https://doi.org/10.1134/S0026893306010110

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  • DOI: https://doi.org/10.1134/S0026893306010110

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