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Dissociation of vitamin D3 and anti-estrogen mediated growth regulation in MCF-7 breast cancer cells

  • Chapter
Molecular and Cellular Effects of Nutrition on Disease Processes

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 26))

Abstract

Our studies have identified 1,25(OH)2D3 as a coordinate regulator of proliferation and apoptosis in breast cancer cells. In MCF-7 cells, 1,25(OH)2D3 down regulates the estrogen receptor (ER), suggesting that the effects of 1,25(OH)2D3 may be linked to disruption of estrogen regulated survival signals. Although studies have demonstrated that 1,25(OH)2D3 inhibits growth of ER negative breast cancer cells, previous data were generated by comparison of cell lines derived from heterogeneous human tumors and harboring diverse genetic alterations. To provide more conclusive evidence for independent growth regulatory pathways mediated by antiestrogens and 1,25(OH)2D3, we examined vitamin D3 sensitivity in MCF-7 cells selected for resistance to ICI 182, 780 (Zeneca, Macclesfield, UK). The clones we selected for resistance to ICI 182,780 retain functional VDR and undergo 1,25(OH)2D3 mediated growth arrest and apoptosis, in vitro and in vivo, despite loss of estrogen dependence. Cell cycle data indicate that treatment of parental or anti-estrogen resistant MCF-7 clones with 1,25(OH)2D3, in the presence or absence of ICI 182,780, increases the percentage of cells in G0/G1 while reducing the number of cells in S phase. In addition, 1,25(OH)2D3 induces characteristic features of apoptosis, including DNA fragmentation, in both parental and anti-estrogen resistant MCF-7 cells. Furthermore, we report that cells selected for vitamin D3 resistance retain sensitivity to ICI 182,780 mediated growth arrest and apoptosis. This work emphasizes that vitamin D3 compounds and anti-estrogens trigger growth arrest and apoptosis in breast cancer cells by distinct mechanisms, and that breast cancer cell sensitivity to 1,25(OH)2D3 is not diminished during the progression to estrogen independence. (Mol Cell Biochem 188: 13-20, 1998)

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References

  1. Chouvet C, Berger U, Coombes RC: 1,25 Dihydroxyvitamin D3 inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20). J Ster Biochem 24: 373–376, 1986

    Article  CAS  Google Scholar 

  2. Colston K, Berger U, Coombes RC: Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet 1: 188–191, 1989

    Article  PubMed  CAS  Google Scholar 

  3. Eisman J, Sutherland RL, McMenemy ML, Fragonas JC, Musgrove EA, Pang G: Effects of 1,25-dihydroxyvitamin D3 on cell cycle kinetics of T47D human breast cancer cells. J Cell Physiol 138: 611–616, 1989

    Article  PubMed  CAS  Google Scholar 

  4. Welsh JE: Induction of apoptosis in breast cancer cells in response to vitamin D and antiestrogens. Biochem Cell Biol 72: 537–545, 1994

    Article  PubMed  CAS  Google Scholar 

  5. Simboli-Campbell M, Narvaez CJ, Tenniswood M, Welsh JE: 1,25(OH)2D3 induces morphological and biochemical indices of apoptosis in MCF-7 breast cancer cells. J Ster Biochem Mol Biol 58: 367–376, 1996

    Article  CAS  Google Scholar 

  6. Simboli-Campbell M, Narvaez CJ, VanWeelden K, Tenniswood M, Welsh JE: Comparative effects of 1,25(OH)2D3 and EB1089 on cell cycle kinetics and apoptosis in MCF-7 cells. Breast Cancer Res Treat 42: 31–41, 1997

    Article  PubMed  CAS  Google Scholar 

  7. James SY, Mackay AG, Colston K: Effects of 1,25 dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Ster Biochem Mol Biol 58: 395–401, 1996

    Article  CAS  Google Scholar 

  8. Simboli-Campbell M, Welsh JE: 1,25 Dihydroxyvitamin D3: Coordinate regulator of active cell death and proliferation in MCF-7 breast cancer cells. In: M. Tenniswood and H. Michna (eds). Apoptosis in Hormone Dependent Cancers. Springer Verlag, Berlin, 1995 pp 181–200

    Chapter  Google Scholar 

  9. Welsh JE, Simboli-Campbell M, Narvaez CJ, Tenniswood M: Role of apoptosis in the growth inhibitory effects of vitamin D in MCF-7 cells. Adv Exper Biol Med 375: 45–52, 1995

    CAS  Google Scholar 

  10. Bursch W, Ellinger A, Kienzl H, Torok L, Pandey S, Sikorska M, Walker R, Schulte Hermann R: Active cell death induced by the anti-estrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: The role of autophagy. Carcinogenesis 17: 1595–1607, 1996

    Article  PubMed  CAS  Google Scholar 

  11. Warri A, Huovinen R, Laine A, Martikainen P, Harkonen P: Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro. J Nat Cancer Inst 85: 1412–1418, 1993

    Article  PubMed  CAS  Google Scholar 

  12. James SY, Mackay A, Binderup L, Colston K: Effects of a new synthetic vitamin D analogue, EB 1089, on the oestrogen responsive growth of human breast cancer cells. J Endocrinol 141: 555–563, 1994

    Article  PubMed  CAS  Google Scholar 

  13. Elstner E, Linker-Israeli M, Said J, Umiel T, de Vos S, Shintaku IP, Heber D, Binderup L, Uskokovic M, Koeffler HP: 20-epi Vitamin D3 analogues: A novel class of potent inhibitors of proliferation and inducers of differentiation of human breast cancer cells. Cancer Res 55: 2822–2830, 1995

    PubMed  CAS  Google Scholar 

  14. Wakeling AK, Dukes M and Bowler J: A potent specific pure antiestrogen with clinical potential. Cancer Res 51: 3867–3873, 1991

    PubMed  CAS  Google Scholar 

  15. Narvaez CJ, VanWeelden K, Byrne I, Welsh JE: Characterization of a vitamin D3 resistant MCF-7 cell line. Endocrinology 137: 400–409, 1996

    Article  PubMed  CAS  Google Scholar 

  16. VanWeelden K, Flanagan L, Binderup L, Tenniswood M, Welsh J: Apoptotic regression of MCF-7 xenografts in nude mice treated with the vitamin D3 analog, EB 1089. Endocrinology 139: 2102–2110, 1998

    Article  PubMed  CAS  Google Scholar 

  17. Kyprianou N, English H, Davidson N, Isaacs J: Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. Cancer Res 51: 162–166, 1991

    PubMed  CAS  Google Scholar 

  18. Navaez CJ, Welsh JE: Differential effects of 1,25-Dihydroxyvitamin D3 and TPA on cell cycle and apoptosis in MCF-7 cells and a vitamin D3 resistant variant. Endocrinology 138: 4690–4698, 1997

    Article  Google Scholar 

  19. Berger U, McClelland R, Wilson P, Greene G, Haussier M, Pike J, Colston K, Easton D, Coombes RC: Immunoctyochemical determination of estrogen receptor, progesterone receptor and l,25(OH)2-vitamin D3 receptor in breast cancer and relationship to prognosis. Cancer Res 51: 239–244, 1991

    PubMed  CAS  Google Scholar 

  20. Abe-Hashimoto J, Kikuchi T, Matsumoto T, Nishii Y, Ogata E, Ikeda K: Antitumor effect of 22-oxa-calcitriol, a noncalcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen. Cancer Res 53: 2534–2537, 1993

    PubMed  CAS  Google Scholar 

  21. Vink-van Wijngaarden T, Pols H, Buurman CJ, van den Bernd, G, Dorssers L, Birkenhager J, van Leeuwen J: Inhibition of breast cancer cell growth by combined treatment with vitamin D3 analogues and tamoxifen. Cancer Res 54: 5711–5717, 1994

    PubMed  CAS  Google Scholar 

  22. Love-Schimenti C, Gibson D, Ratnam A and Bikle D: Antiestrogen potentiation of antiproliferative effects of vitamin D3 analogues in breast cancer cells. Cancer Res 56: 2789–2794, 1996

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. W. Alton Jones Cell Science Center, Lake Placid, New York, USA

    Elizabeth Nolan, Manjula Donepudi, Kathryn VanWeelden, Louise Flanagan & JoEllen Welsh

  2. Clarkson University, Potsdam, New York, USA

    Kathryn VanWeelden

  3. University College Dublin, Ireland

    Louise Flanagan

Authors
  1. Elizabeth Nolan
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  2. Manjula Donepudi
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  3. Kathryn VanWeelden
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  4. Louise Flanagan
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  5. JoEllen Welsh
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Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, Manitoba, Canada, R2H 2A6

    Grant N. Pierce

  2. Department of Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara Kanagawa 228, Japan

    Tohru Izumi (Professor and Chairman) (Professor and Chairman)

  3. Medizinische Forschung Philipps University of Marburg, Karl-von-Frisch-Str., 135033, Marburg, Germany

    Heinz Rupp

  4. INRA, Lipides Membranaires et Fonctions Cardiovasculaires Faculté des Sciences Pharmaceutiques et Biologiques, 4 Av de l’Observatoire, 75270, Paris Cedex 06, France

    Alain Grynberg

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© 1998 Springer Science+Business Media Dordrecht

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Nolan, E., Donepudi, M., VanWeelden, K., Flanagan, L., Welsh, J. (1998). Dissociation of vitamin D3 and anti-estrogen mediated growth regulation in MCF-7 breast cancer cells. In: Pierce, G.N., Izumi, T., Rupp, H., Grynberg, A. (eds) Molecular and Cellular Effects of Nutrition on Disease Processes. Developments in Molecular and Cellular Biochemistry, vol 26. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5763-0_2

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  • DOI: https://doi.org/10.1007/978-1-4615-5763-0_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7641-5

  • Online ISBN: 978-1-4615-5763-0

  • eBook Packages: Springer Book Archive

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