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Secretion of breast gross cystic disease fluid proteins by T47D breast cancer cells in culture — modulation by steroid hormones

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Summary

The effect of steroid hormones on modulating the secretion rates of three human breast gross cystic disease fluid proteins (GCDFP-15, GCDFP-24, and GCDFP-44) by T47D breast carcinoma cells in tissue culture was evaluated. Androgens (dihydrotestosterone or fluoxymesterone) were capable of stimulating the secretion rates for all three GCDFP's while showing a minimal trend toward slowing the growth rate of T47D cells. This is the first study which shows that androgens can specifically stimulate all three of the major breast GCDFP's concomitantly. Progesterone, and three synthetic progestins, all showed inhibition of the growth rate of T47D cells while causing enhancement of the secretion of GCDFP-15 and GCDFP-44, and only minimal effect on the secretion rate of GCDFP-24. Estradiol was essentially neutral to the growth rate of the T47D cells in our test system. Estradiol did cause a mild enhancement of GCDFP-44 secretion rate, with no appreciable effect on GCDFP-15 or GCDFP-24 secretion rates. These findings suggest that an androgenic stimulus may be involved in the secretion of GCDFP's associated with breast gross cystic disease.

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References

  1. Haagensen CD: Diseases of the Breast, 3rd Edition. WB Saunders Publishing Co, Philadelphia, 1986, pp 250–266

    Google Scholar 

  2. Haagensen DE Jr: Is cystic disease related to breast cancer? Am J Surg Path 15: 687–694, 1991

    PubMed  Google Scholar 

  3. Harrington E, Lesnick G: The association between gross cysts of the breast and breast cancer. Breast 7: 13–17, 1980

    Google Scholar 

  4. Jones BM, Bradbeer JW: The presentation and progress of macroscopic breast cysts. Brit J Surg 67: 669–671, 1980

    PubMed  Google Scholar 

  5. Roberts MM, Jones V, Elton RA, Fortt RW, Williams W, Gravelle IH: Risk of breast cancer in women with a history of benign disease of the breast. Brit Med J 288: 275–278, 1984

    Google Scholar 

  6. Hutchinson WB, Thomas DB, Hamlin WB, Roth GJ, Peterson AV, Williams B: Risk of breast cancer in women with benign breast disease. J Natl Cancer Inst 65: 13–20, 1980

    PubMed  Google Scholar 

  7. Dupont WD, Page DL: Risk factors for breast cancer in women with proliferative breast disease. New Eng J Med 312: 146–151, 1985

    PubMed  Google Scholar 

  8. Haagensen CD: Diseases of the Breast, 3rd Edition. WB Saunders Publishing Co, Philadelphia, 1986, pp 82–101

    Google Scholar 

  9. Wellings SR, Alpers CE: Apocrine cystic metaplasia: subgross pathology and prevalence in cancer associated versus random autopsy breasts. Human Path 18: 381–386, 1987

    Google Scholar 

  10. Bradlow HL, Rosenfeld RS, Kream J, Fleisher M, O'Connor J, Schwartz MK: Steroid hormone accumulation in human breast cyst fluid. Cancer Res 41: 105–107, 1981

    Google Scholar 

  11. Miller WR, Roberts MM, Creel RJ, Yap PL, Kelly RW, Forrest APM: Androgen conjugates in human breast cyst fluids. J Natl Cancer Inst 69: 1055–1058, 1982

    PubMed  Google Scholar 

  12. Vanluchene E, Vandekerckhove D, De Boever J, Sandra P: Structures and concentrations of fifteen different steroid sulfates in human breast cyst fluids. J Steroid Biochem 21: 367–371, 1984

    PubMed  Google Scholar 

  13. Belanger A, Caron S, Labrie F, Naldoni C, Dogliotti L, Angeli A: Levels of eighteen non-conjugated and conjugated steroids in human breast cyst fluid: relationship to cyst type. Eur J Cancer 26: 277–281, 1990

    PubMed  Google Scholar 

  14. Pearlman WH, Gueriguian JL, Sawyer ME: A specific progester-one-binding component of human breast cyst fluid. J Biol Chem 248: 5736–5741, 1973

    PubMed  Google Scholar 

  15. Haagensen DE Jr, Mazoujian GM, Dilley WG, Pedersen CE, Kister SJ, Wells SA Jr: Breast gross cystic disease fluid analysis. I. Isolation and radioimmunoassay for a major component protein. J Natl Cancer Inst 62: 239–247, 1979

    PubMed  Google Scholar 

  16. Haagensen DE Jr, Mazoujian G: Biochemistry and immunohistochemistry of gross cystic disease fluid proteins of the breast. In: Haagensen CD (ed) Diseases of the Breast, 3rd Edition, W.B. Saunders Publishing Co, Philadelphia, 1986, pp 474–500

    Google Scholar 

  17. Vandewalle B, Hornez L, Vennin P, Peyrat JP, Lefebvre J: Further characterization of the light breast cyst fluid protein GCDFP-15. Biochemie 68: 649–656, 1986

    Google Scholar 

  18. Lea OA: Binding properties of progesterone-binding cyst protein PBCP. Steroids 52: 333–338, 1988

    PubMed  Google Scholar 

  19. Balbin M, Freije JMP, Fueyo A, Sanchez LM, Lopez-Otin C: Apolipoprotein D is the major component protein in cyst fluid from women with human breast gross cystic disease. Biochem J 271: 803–807, 1990

    PubMed  Google Scholar 

  20. Dilley WG, Haagensen DE Jr, Cox CE, Wells SA Jr: Immunologic and steroid binding properties of the GCDFP-24 protein isolated from human breast gross cystic disease fluid. Breast Cancer Res Treat 16: 253–260, 1990

    PubMed  Google Scholar 

  21. Battaglia F, Rossi S, Scambia G, Lanzone A, Benedetti-Panice P, Ferrandina G, Lombardi CP, Bellantone R, Crucitti F, Mancuso S: Epidermal growth factor levels in human breast cyst fluid. Anticancer Res 9: 1661–1664, 1989

    PubMed  Google Scholar 

  22. Haagensen DE Jr, Dilley WG, Mazoujian G, Wells SA Jr: Review of GCDFP-15: an apocrine marker protein. Ann NY Acad Sci 586: 161–173, 1990

    PubMed  Google Scholar 

  23. Pearlman WH, Peng LH, Mazoujian G, Haagensen DE Jr, Wells SA Jr: A specific progesterone-binding component of human breast cyst fluid. Its isolation and characterization. J Endrocrinology 75: 19p-20p, 1977

    Google Scholar 

  24. Kelton CA, Monahan JE: Androgen induction of CDP mRNA, a human breast tumor marker (abstract). Advances in Gene Technology — Molecular Biology of the Endocrine System. ISCO Short Reports, Cambridge Univ Press, Cambridge, England, 4: 300–301, 1986

    Google Scholar 

  25. Myal Y, Gregory C, Wang H, Hamerton JL, Shiu RPC: The gene for prolactin inducible protein, uniquely expressed in exocrine organs, maps to chromosome 7. Somatic and Molecular Genetics 15: 265–270, 1989

    Google Scholar 

  26. Simard J, Veilleux R, de Launoit Y, Haagensen DE, Labrie F: Stimulation of apolipoprotein D secretion by steroids coincides with inhibition of cell proliferation in human LNCaP prostate cancer cells. Cancer Res 51: 4336–4341, 1991

    PubMed  Google Scholar 

  27. Mazoujian G, Pinkus GS, Davis S, Haagensen DE Jr: Immunohistochemistry of a breast gross cystic disease fluid protein (GCDFP-15): A marker of apocrine epithelium and breast carcinomas with apocrine features. Am J Path 110: 105–112, 1983

    PubMed  Google Scholar 

  28. Mazoujian G, Haagensen DE Jr: The immunopathology of gross cystic disease fluid proteins. Ann NY Acad Sci 586: 188–197, 1990

    PubMed  Google Scholar 

  29. Mazoujian G: Immunohistochemistry of GCDFP-24 and Zn-alpha-2-glycoprotein in benign sweat gland tumors. Am J Dermatopath 12: 452–457, 1990

    PubMed  Google Scholar 

  30. Bundred NJ, Miller WR, Walker R: An immuno-histological study of the breast cyst fluid protein, Zn-alpha-2-glycoprotein. Histopathology 11: 603–610, 1987

    PubMed  Google Scholar 

  31. Gagnon S, Tetu B, Dube J-Y, Tremblay RR: Expression of Znalpha-2-glycoprotein and PSP-94 in prostatic adenocarcinoma. An immunohistochemical study of 88 cases. Am J Path 136: 1147–1152, 1990

    PubMed  Google Scholar 

  32. Mazoujian G, Bodian C, Haagensen DE Jr, Haagensen CD: Expression of GCDFP-15 in breast carcinomas: relationship to pathologic and clinical factors. Cancer 63: 2156–2161, 1989

    PubMed  Google Scholar 

  33. Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT: Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. Human Path 20: 281–287, 1989

    Google Scholar 

  34. Horwitz KB, Zava DT, Thilagar AK, Jansen E, McGuire WL: Steroid receptor analysis of nine human breast cancer lines. Cancer Res 38: 2434–2442, 1978

    Google Scholar 

  35. Keydar I, Chen L, Karby S, Weiss FR, Delarea J, Radu M, Chaitcik S, Brenner HJ: Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer 15: 659–670, 1979

    PubMed  Google Scholar 

  36. Haagensen CD, Bodian C, Haagensen DE Jr: Breast Carcinoma — Risk and Detection. W.B. Saunders Publishing Co, Philadelphia, 1986, pp 300–338

    Google Scholar 

  37. Fraker PJ, Speck JC: Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetra-chloro-3a,6a-di-phenylglycoluril. Biochem Biophys Res Commun 80: 849–857, 1978

    PubMed  Google Scholar 

  38. Haagensen DE Jr, Wells SA Jr, Haider M: Analysis of human breast gross cystic disease fluid protein (GCDFP-15) by isotope dilution RIA with a solid phase (Kynar) second antibody (abstract). Proc Am Assoc Clin Chem 26: 980, 1980

    Google Scholar 

  39. Newman ES, Moskie LA, Duggal RN, Goldenberg DM, Hansen HJ: Murine monoclonal antibody adsorbed onto vinylidene fluoride floccules used to eliminate antibody interference in ‘sandwich’-type immunoassays. Clin Chem 35: 1743–1746, 1989

    PubMed  Google Scholar 

  40. Fiszer-Szafarz B, Szafarz D, Guevara de Murillo A: A general, fast, and sensitive micromethod for DNA determination: application to rat and mouse liver, rat hepatoma, human leukocytes, chicken fibroblasts, and yeast cells. Anal Biochem 110: 165–170, 1981

    PubMed  Google Scholar 

  41. Chalbos D, Vignon F, Keydar I, Rochefort H: Estrogens stimulate cell proliferation and induce secretory proteins in a human breast cancer cell line (T47D). J Clin Endocrin Metab 55: 276–283, 1982

    Google Scholar 

  42. Horwitz KB, Freidenberg GR: Growth inhibition and increase of insulin receptors in antiestrogen-resistant T47Dco human breast cancer cells by progestins: implications for endocrine therapies. Cancer Res 45: 167–173, 1985

    Google Scholar 

  43. Sutherland RL, Hall RE, Pang GYN, Musgrove EA, Clarke CL: Effect of medroxyprogesterone acetate on proliferation and cell cycle kinetics of human mammary carcinoma cells. Cancer Res 48: 5084–5091, 1988

    Google Scholar 

  44. Reese CC, Warshaw ML, Murai JT, Siiteri PK: Alternative models for estrogen and androgen regulation of human breast cancer cell (T47D) growth. Ann NY Acad Sci 538: 112–120, 1988

    PubMed  Google Scholar 

  45. Chalbos D, Rochefort H: Dual effects of the progestin R5020 on proteins released by the T47D human breast cancer cells. J Biol Chem 259: 1231–1238, 1984

    PubMed  Google Scholar 

  46. Chalbos D, Haagensen DE Jr, Parish T, Rochefort H: Identification and androgen regulation of two proteins released by T47D human breast cancer cells. Cancer Res 47: 2787–2792, 1987

    Google Scholar 

  47. Simard J, Dauvois S, Haagensen DE Jr, Levesque C, Merand Y, Labrie F: Regulation of progesterone-binding breast cyst protein GCDFP-24 secretion by estrogens and androgens in human breast cancer cells: a new marker of steroid action in breast cancer. Endocrinology 126: 3223–3231, 1990

    PubMed  Google Scholar 

  48. Simard J, Hatton AC, Labrie C, Dauvois S, Zaho HF, Haagensen DE Jr, Labrie F: Inhibitory effect of estrogens on GCDFP-15 mRNA levels and secretion in ZR-75-1 human breast cancer cells. Mol Endocrinol 3: 694–702, 1989

    PubMed  Google Scholar 

  49. Hissom JR, Moore MR: Progestin effects on growth in human breast cancer cell line T47D-possible therapeutic implications. Biochem Biophys Res Commun 145: 706–711, 1987

    PubMed  Google Scholar 

  50. Hissom JR, Bowden RT, Moore MR: Effects of progestins, estrogens, and antihormones on growth and lactate dehydrogenase in the human breast cancer cell line T47D. Endocrinology 125: 418–423, 1989

    PubMed  Google Scholar 

  51. Glover JF, Irwin JT, Darbre PD: Interaction of phenol red with estrogenic and antiestrogenic action on growth of human breast cancer cells ZR-75-1 and T47D. Cancer Res 48: 3693–3697, 1988

    PubMed  Google Scholar 

  52. Labrie C, Plante CM, La Pointe S, Labrie F: Analysis of the androgenic activity of synthetic ‘progestins’ currently used for the treatment of prostate cancer. J Steroid Biochem 28: 379–384, 1987

    PubMed  Google Scholar 

  53. Luthy IA, Begin DJ, Labrie F: Androgenic activity of synthetic progestins and spironolactone in androgen-sensitive mouse mammary carcinoma (Shionogi) cells in culture. J Steroid Biochem 31: 845–852, 1988

    PubMed  Google Scholar 

  54. Poulin R, Baker D, Poirier D, Labrie F: Androgen and glucocorticoid receptor-mediated inhibition of cell proliferation by medroxyprogesterone acetate in ZR75 human breast cancer cells. Breast Cancer Res Treat 13: 161–172, 1989

    PubMed  Google Scholar 

  55. Soto AM, Murai JT, Siiteri PK, Sonnenschein C: Control of cell proliferation: evidence for negative control on estrogen-sensitive T47D human breast cancer cells. Cancer Res 46: 2271–2275, 1986

    PubMed  Google Scholar 

  56. Wang Y, Miksicek RJ: Identification of a dominant negative form of the human estrogen receptor. Mol Endocrinol 5: 1707–1715, 1991

    PubMed  Google Scholar 

  57. England PC, Sellwood RA, Knyba RE, Irvine JDB: Serum androgen levels and the menstrual cycle in women with benign or malignant breast disease. Clin Oncology 7: 213–219, 1981

    Google Scholar 

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Haagensen, D.E., Stewart, P., Dilley, W.G. et al. Secretion of breast gross cystic disease fluid proteins by T47D breast cancer cells in culture — modulation by steroid hormones. Breast Cancer Res Tr 23, 77–86 (1992). https://doi.org/10.1007/BF01831479

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