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Transformation of estrone and estradiol in hormone-dependent and hormone-independent human breast cancer cells

Effects of the antiestrogen ICI 164,384, danazol, and promegestone (R-5020)

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Summary

Using different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, Hs-578S, MDA-MB-436) human breast cancer cells, the interconversion estrone (E1) ⇌ estradiol (E2) was explored. The data show very clearly that in the hormone-dependent cells the tendency is to form E2 after incubation with E1, whereas after incubation with E2 most of this estrogen remains unchanged. In the hormone-independent cells, in contrast most of E1 remains E1, while E2 is converted into E1. The tendency of the reductive ⇌ oxidative direction is supported by the analysis of estrogens in the culture medium. To explore the possible action of different drugs on the 17β-hydroxysteroid dehydrogenase (17β-HSD) activity, it was observed that the potent antiestrogen ICI 164,384 inhibits the conversion of E1 to E2, while a lesser effect is observed with Danazol and only weak inhibition is obtained with the progestagen Promegestone (R-5020). It is concluded that the orientation of 17β-HSD activity for the interconversion E1 ⇌ E2 in hormone-dependent and -independent cells is related to the hormonal status of the cells.

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References

  1. Segaloff A: Hormones and mammary carcinogenesis. In: McGuire WL (ed) Breast Cancer 2: Advances in Research and Treatment. Plenum, New York, 1978, pp 1–22

    Google Scholar 

  2. Kirschner MA: The role of hormones in the development of human breast cancer. In: McGuire WL (ed) Breast Cancer 2: Advances in Research and Treatment. Plenum, New York, 1978, pp 199–226

    Google Scholar 

  3. Lippman ME, Dickson RB, Bates S, Knabbe C, Huff K, Swain S, McManaway M, Bronzert D, Kasid A, Gelmann EP: Autocrine and paracrine growth regulation of human breast cancer. Breast Cancer Res Treat 7: 59–70, 1986

    Google Scholar 

  4. Miller WR, Forrest APM, Hamilton T: Steroid metabolism by human breast and rat mammary carcinoma. Steroids 23: 379–395, 1974

    Google Scholar 

  5. Lipton A, Santner SJ, Santen RJ, Harvey HA, Feil PD, White-Hershey D, Bartholomew MJ, Antle CE: Aromatase activity in primary and metastatic human breast cancer. Cancer 59: 779–782, 1987

    Google Scholar 

  6. Perel E, Danilescu D, Kharlip L, Blackstein M, Killinger DW: Steroid modulation of aromatase activity in human cultured breast carcinoma cells. J Steroid Biochem 29: 393–399, 1988

    Google Scholar 

  7. Vignon F, Terqui M, Westley B, Derocq D, Rochefort H: Effects of plasma estrogen sulfates in mammary cancer cells. Endocrinology 106: 1079–1086, 1980

    Google Scholar 

  8. Pasqualini JR, Gelly C, Lecerf F: Estrogen sulfates: biological and ultrastructural responses and metabolism in MCF-7 human breast cancer cells. Breast Cancer Res Treat 8: 233–240, 1986

    Google Scholar 

  9. Pasqualini JR, Gelly C, Nguyen B-L, Vella C: Importance of estrogen sulfates in breast cancer. J Steroid Biochem 34: 155–163, 1989

    Google Scholar 

  10. Santner SJ, Feil PD, Santen RJ:In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importanceversus the aromatase pathway. J Clin Endocrinol Metab 59: 29–33, 1984

    Google Scholar 

  11. Pasqualini JR, Schatz B, Varin C, Nguyen B-L: Recent data on estrogen sulfatase and sulfotransferase activities in human breast cancer. J Steroid Biochem Molec Biol 41: 323–329, 1992

    Google Scholar 

  12. Abul-Hajj YJ, Iverson R, Kiang DT: Estradiol 17β-dehydrogenase and estradiol binding in human mammary tumors. Steroids 33: 477–484, 1979

    Google Scholar 

  13. Bonney RC, Reed MJ, Davidson K, Beranek PA, James VHT: The relationship between 17β-hydroxysteroid dehydrogenase activity and oestrogen concentrations in human breast tumours and in normal breast tissue. Clin Endocrinol 19: 727–739, 1983

    Google Scholar 

  14. Adams EF, Coldham NG, James VHT: Steroidal regulation of oestradiol-17β dehydrogenase activity of the human breast cancer cell line MCF-7. J Endocrinol 118: 149–154, 1988

    Google Scholar 

  15. McNeill JM, Reed MJ, Beranek PA, Bonney RC, Ghilchik MW, Robinson DJ, James VHT: A comparison ofin vivo uptake and metabolism of3H-oestrone and3H-oestradiol by normal breast and breast tumour tissues in post-menopausal women. Int J Cancer 38: 193–196, 1986

    Google Scholar 

  16. Tseng L, Gurpide E: Induction of human endometrial estradiol dehydrogenase by progestins. Endocrinology 97: 825–833, 1975

    Google Scholar 

  17. Tseng L, Mazella J, Tseng L: Kinetic studies of human endometrial hydroxysteroid dehydrogenase. J Steroid Biochem 14: 437–442, 1981

    Google Scholar 

  18. Coldham NG, James VHT: A possible mechanism for increased breast cell proliferation by progestins through increased reductive 17β-hydroxysteroid dehydrogenase activity. Int J Cancer 45: 174–178, 1990

    Google Scholar 

  19. Couture P, Theriault C, Simard J, Labrie F: Androgen receptor-mediated stimulation of 17β-hydroxysteroid dehydrogenase activity by dihydrotestosterone and medroxy-progesterone acetate in ZR-75-1 human breast cancer cells. Endocrinology 132: 179–185, 1993

    Google Scholar 

  20. Burton K: A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62: 315–323, 1956

    Google Scholar 

  21. Bearden JC Jr: Quantitation of submicrogram quantities of protein by an improved protein-dye binding assay. Biochim Biophys Acta 533: 525–531, 1978

    Google Scholar 

  22. Lineweaver H, Burk D: The determination of enzyme dissociation constants. J Am Chem Soc 56: 658–666, 1934

    Google Scholar 

  23. Pasqualini JR, Gelly C: Effect of tamoxifen and tamoxifen derivatives on the conversion of estrone sulfate to estradiol in the MCF-7 mammary cancer cell line. Cancer Lett 40: 115–121, 1988

    Google Scholar 

  24. Pasqualini JR, Nguyen B-L: Estrone sulfatase activity and effect of antiestrogens on transformation of estrone sulfate in hormone-dependent vs. independent human breast cancer cell lines. Breast Cancer Res Treat 18: 93–98, 1991

    Google Scholar 

  25. Chetrite G, Varin C, Delalonde L, Pasqualini JR: Effect of Promegestone, Tamoxifen, 4-hydroxytamoxifen and ICI 164,384 on the oestrone sulphatase activity of human breast cancer cells. Anticancer Res 13: 931–934, 1993

    Google Scholar 

  26. Nguyen B-L, Ferme I, Chetrite G, Pasqualini JR: Action of Danazol on the conversion of estrone sulfate to estradiol and on the sulfatase activity in the MCF-7, T-47D and MDA-MB-231 human mammary cancer cells. J Steroid Biochem Molec Biol 46: 17–23, 1993

    Google Scholar 

  27. Luu-The V, Labrie C, Simard J, Lachance Y, Zhao H-F, Couet J, Leblanc G, Labrie F: Structure of two in tandem human 17β-hydroxysteroid dehydrogenase genes. Molec Endocrinol 4: 268–275, 1990

    Google Scholar 

  28. Isomaa VV, Ghersevich SA, Maentausta OK, Peltoketo EH, Poutanen MH, Vihko RK: Steroid biosynthetic enzymes: 17β-hydroxysteroid dehydrogenase. Ann Med 25: 91–97, 1993

    Google Scholar 

  29. Poutanen M, Moncharmont B, Vihko R: 17β-hydroxysteroid dehydrogenase gene expression in human breast cancer cells: regulation of expression by a progestin. Cancer Res 52: 290–294, 1992

    Google Scholar 

  30. Singh A, Reed MJ: Insulin-like growth factor Type I and insulin-like growth factor Type II stimulate oestradiol-17β-hydroxysteroid dehydrogenase (reductive) activity in breast cancer cells. J Endocrinol 129: R5–R8, 1991

    Google Scholar 

  31. Malet C, Vacca A, Kuttenn F, Mauvais-Jarvis P: 17β-estradiol dehydrogenase (E2DH) activity in T47D cells. J Steroid Biochem Molec Biol 39: 769–775, 1991

    Google Scholar 

  32. Pollow K, Boquoi E, Baumann J, Schmidt-Gollwitzer M, Pollow B: Comparison of thein vitro conversion of estradiol-17β to estrone of normal and neoplastic human breast tissue. Molec Cell Endocrinol 6: 333–348, 1977

    Google Scholar 

  33. van Landeghem AAJ, Poortman J, Nabuurs M, Thijssen JHH: Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res 45: 2900–2906, 1985

    Google Scholar 

  34. Vermeulen A, Deslypere JP, Paridaens R, Leclercq G, Roy F, Heuson JC: Aromatase, 17β-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in post-menopausal women. Eur J Cancer Clin Oncol 22: 515–525, 1986

    Google Scholar 

  35. Santner SJ, Santen RJ: Inhibition of estrone sulfatase and 17β-hydroxysteroid dehydrogenase by antiestrogens. J Steroid Biochem Molec Biol 45: 383–390, 1993

    Google Scholar 

  36. Mann VZ, Newton CJ, Tait GH: 17β-hydroxysteroid dehydrogenases in human breast tissues: purification and characterization of soluble enzymes and the distribution of particulate and soluble forms in adipose, non-adipose and tumour tissues. J Molec Endocrinol 7: 45–55, 1991

    Google Scholar 

  37. Mehta RR, Das Gupta TK: Regulation of 17β-hydroxysteroid dehydrogenase in a newly-established human breast carcinoma cell line. J Steroid Biochem Molec Biol 46: 623–629, 1993

    Google Scholar 

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Authors and Affiliations

  1. Foundation for Hormone Research, C.N.R.S. Steroid Hormone Research Unit, 26 Boulevard Brune, 75014, Paris, France

    Bach-Lien Nguyen, Gérard Chetrite & Jorge Raul Pasqualini

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  1. Bach-Lien Nguyen
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  2. Gérard Chetrite
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  3. Jorge Raul Pasqualini
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Nguyen, BL., Chetrite, G. & Pasqualini, J.R. Transformation of estrone and estradiol in hormone-dependent and hormone-independent human breast cancer cells. Breast Cancer Res Tr 34, 139–146 (1995). https://doi.org/10.1007/BF00665786

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