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Collagen gel culture system and analysis of estrogen effects on mammary carcinogenesis

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Abstract

The results obtained to date from studies dealing with the role of hormones, including estrogen, on growth of mammary epithelial cells inside the collagen gel are described. The collagen gel matrix culture system appears to be a suitable system to obtain in vivo-like effects of hormones on mammary cell in vitro. The results thus far indicate that prolactin along with progesterone or cortisol can stimulate mammary cell proliferation. Thus far, estrogen has not been found to be mitogenic in our in vitro system.

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References

  • Alexander P, Horning E (1958) Observations on the Oppenheimer method of inducing tumors by subcutaneous implantation of plastic films. In: Wolstenholme G, O'Connor M (eds) Little, Brown, Boston (Carcinogenesis, Mechanisms of Action, p 12)

    Google Scholar 

  • Allegra JC, Lippman ME (1978) Growth of a human breast cancer cell line in serum-free hormone-supplemented medium. Cancer Res 38: 3823–3829

    Google Scholar 

  • Barrett JC, Wong A, McLachlan JA (1981) Diethylstilbestrol induces neoplastic transformation without measurable gene mutation at two loci. Science 212: 1402–1404

    Google Scholar 

  • Beatson GT (1896) On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment, with illustrative cases. Lancet II: 104–107

    Google Scholar 

  • Bresciani F (1965) Effect of ovarian hormones on duration of DNA synthesis in cells of the C3H mouse mammary gland. Exp Cell Res 38: 13–32

    Google Scholar 

  • Chalbos D, Vignon F, Keydar I, Rochefort H (1982) Estrogen stimulates cell proliferation and induces secretory proteins in a human breast cancer cell line (T47D). J Clin Endocrinol Metab 55: 276–283

    Google Scholar 

  • Chen L, Lindner HR, Lancet M (1973) Mitogenic action of estradiol-17β on human myometrial and endometrial cells in long-term tissue cultures. J Endocrinol 59: 87–97

    Google Scholar 

  • Dao TL (1971) Inhibition of tumor induction in chemical carcinogenesis in the mammary gland. Progr Exp Tumor Res 14: 59–88

    Google Scholar 

  • Dao TL (1981) The role of ovarian steroid hormones in mammary carcinogenesis. Banbury Rep 8: 281–298

    Google Scholar 

  • Darbre P, Yates J, Curtis S, King RJB (1983) Effect of estradiol on human breast cancer cells in culture. Cancer Res 43: 349–354

    Google Scholar 

  • Edery M, Imagawa W, Larson L, Nandi S (1983) Unpublished

  • Furth J (1975) Hormones as etiological agents in neoplasia. In: Becker FF (ed) Plenum Press, New York (Cancer, A Comprehensive Treatise Vol 1, p 75)

    Google Scholar 

  • Gardner WU, Pfeiffer CA, Trentin JJ (1959) Hormonal factors in experimental carcinogenesis. In: Homburger F (ed) Harper & Row, New York (The Physiopathology of Cancer, p 152)

    Google Scholar 

  • Gerschenson LE, Conner E, Murai JT (1977) Regulation of the cell cycle by diethylstilbestrol and progesterone in cultured endometrial cells. Endocrinol 100: 1468–1471

    Google Scholar 

  • Greenwald P, Barolom JJ, Nasca PC (1971) Vaginal cancer after maternal treatment with synthetic estrogens. N Eng J Med 285: 390–392

    Google Scholar 

  • Herbst AL, Ulfelder H, Poskanzer DC (1971) Adenocarcinoma of the vagina: Association of maternal stilbesterol therapy with tumor appearance in young women. N Engl J Med 284: 878–881

    Google Scholar 

  • Hoover R, Glass A, Finkle WD, Azavedo D, Milne K (1981) Conjugated estrogen and breast cancer risk in women. J Natl Cancer Inst 67: 815–820

    Google Scholar 

  • Huseby RA (1965) Steroids and tumorigenesis in experimental animals. In: Dorfman RI (ed) Academic Press, New York (Methods in Hormone Research Vol 4, p 123)

    Google Scholar 

  • Huseby RA (1980) Demonstration of a direct carcinogenic effect of estradiol on Leydig cells of the mouse. Cancer Res 40: 1006–1013

    Google Scholar 

  • Iguchi T, Uchima F-DA, Ostrander PL, Bern HA (1983) Growth of normal mouse vaginal epithelial cells in and on collagen gels. Proc Natl Acad Sci (USA) 80: 3743–3747

    Google Scholar 

  • Imagawa W (1983) Lipid regulation of the growth of normal and tumor mouse mammary epithelial cells in serum-free collagen gel culture. Breast Cancer Research Conf: Proc of Int Symp held in Denver, CO, March 20–24, p 35

  • Imagawa W, Tomooka Y, Edery M, Nandi S (1983a) Unpublished

  • Imagawa W, Tomooka Y, Nandi S (1982) Serum-free growth of normal and tumor mouse mammary epithelial cells in primary culture. Proc Natl Acad Sci USA 79: 4074–4077

    Google Scholar 

  • Imagawa W, Tomooka Y, Yang J, Guzman R, Richards J, Nandi S (1983b) The isolation and serum-free cultivation of mammary epithelial cells within a collagen gel matrix. In: Barnes D, Sirbasku D, Sato G (eds) Alan R Liss, Inc, New York (Methods in Molecular and Cellular Biology), in press

    Google Scholar 

  • Jensen EV, DeSombre ER (1972) Mechanism of action of the sex hormones. Ann Rev Biochem 41: 203–230

    Google Scholar 

  • Jones LA, Bern HA (1979) Cervicovaginal and mammary gland abnormalities in BALB/cCrgl mice treated neonatally with progesterone and estrogen, alone or in combination. Cancer Res 39: 2560–2567

    Google Scholar 

  • Kennedy AR, Weichselbaum RR (1981) Effects of 17β-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors. Carcinogenesis 2: 67–69

    Google Scholar 

  • Kirkman H (1959) Estrogen-induced tumors of the kidney in Syrian hamsters. Natl Cancer Inst Monogr 1: 1–59

    Google Scholar 

  • Lacassagne A (1932) Apparition de cancers de la mamelle chez la souris male, soumise à des injections de folliculine. CR Hebd Seances Acad Sci 195: 630–632

    Google Scholar 

  • Laugier C, Pageaux J-F, Soto AM, Sonnenschein C (1983) Mechanism of estrogen action: Indirect effect of estradiol-17β on proliferation of quail oviduct cells. Proc Natl Acad Sci USA 80: 1621–1625

    Google Scholar 

  • Lemon HM (1982) Estrogen. In: Holland JF, Frei E (eds) Lea and Febiger, Philadelphia (Cancer Medicine, p 967)

    Google Scholar 

  • Liehr JG, DaGue BB, Ballatore AM, Sirkasku DA (1982) Multiple roles of estrogen in estrogen-dependent renal clear cell carcinoma of Syrian hamster. Cold Spring Harbor Conf on Cell Prolif 9: 445–458

    Google Scholar 

  • Lingeman CH (1979) Hormones and hormonomimetic compounds in the etiology of cancer. In: Lingeman CH (ed) Springer, Berlin (Carcinogenic hormones. Recent Results in Cancer Research, Vol 66, p 1)

    Google Scholar 

  • Lippman M (1981) Hormonal regulation of human breast cancer cells in vitro. Banbury Rep 8: 171–181

    Google Scholar 

  • Leung BS, Qureshi S, Leung JS (1982) Response to estrogen by the human mammary carcinoma cell line CAMA-I. Cancer Res 42: 5060–5066

    Google Scholar 

  • Maurer HR, Round DE, Raiborn CW (1967) Effects of oestradiol on calf endometrial tissue in vitro. Nature (Lond) 213: 182–183

    Google Scholar 

  • McGrath CM (1983) Augmentation of the response of normal mammary epithelial cells to estradiol by mammary stroma. Cancer Res 43: 1355–1360

    Google Scholar 

  • McGrath MF, Palmer S (1983) Effect of mammogenic hormones and growth factors on growth of rat mammary epithelial cells in collagen gel culture. Breast Cancer Res Conf: Proc of Int Symp held in Denver, CO March 20–24. 1983, p 58

  • McGrath MF, Palmer S, Nandi S (1983) Effects of hormones and growth factors on the proliferation of rat mammary epithelial cells cultured in collagen gel matrix. Submitted

  • McLachlan JA, Dixon RL (1976) Transplacental toxicity of diethylstilbesterol: a special problem in safety evaluation. Adv Mod Toxicol (Part I) I: 423–448

    Google Scholar 

  • McLachlan JA, Wong A, Degen GH, Barrett CJ (1982) Morphological and neoplastic transformation of Syrian hamster embryo fibroblasts by diethylstilbesterol and its analogs. Cancer Res 42: 3040–3045

    Google Scholar 

  • Metzler M (1981) The metabolism of diethylstilbesterol. CRC Crit Rev Biochem 10: 171–212

    Google Scholar 

  • Nandi S (1978) Role of hormones in mammary neoplasia. Cancer Res 38: 4046–4049

    Google Scholar 

  • Nandi S, Imagawa W, Tomooka Y, Shiurba R, Yang J (1982) Mammogenic hormones: possible roles in vivo. Cold Spring Harbor Conf Cell Prolif 9: 779–788

    Google Scholar 

  • Nandi S, Yang J, Richards J, Guzman R (1981) Role of hormones in mammogenesis and carcinogenesis. Banbury Rep 8: 445–453

    Google Scholar 

  • Nandi S, Yang J, Richards J, Guzman R, Rodriguez R, Imagawa W (1980) Role of growth factors and classical hormones in the control of growth and function of mammary tissues. In: Ishi S, Hirano T, Wada M (eds) Japan Scientific Press, Tokyo (Hormones, Adaptation and Evolution, p 145)

    Google Scholar 

  • Noble RL (1964) Tumors and hormones. In: Pincus G, Thimann KV, Astwood EB (eds) Academic Press, New York (The Hormones, p 559)

    Google Scholar 

  • Noble RL, Cutts JH (1959) Mammary tumors of the rat: a review. Cancer Res 19: 1125–1139

    Google Scholar 

  • Page MJ, Field JK, Everett NP, Green CD (1983) Serum regulation of the estrogen responsiveness of the human breast cancer cell line MCF-7. Cancer Res 43: 1244–1250

    Google Scholar 

  • Pasco D, Quan A, Smith S, Nandi S (1982) Effect of hormones and EGF in proliferation of rat mammary epithelium enriched for alveoli — an in vitro study. Exp Cell Res 141: 313–324

    Google Scholar 

  • Pienta RJ, Poiley JA, Lebherz WB (1977) Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary culture as a reliable in vitro bioassay for identifying diverse carcinogens. Int J Cancer 19: 624–655

    Google Scholar 

  • Richards J, Guzman R, Konrad M, Yang J, Nandi S (1982a) Growth of mouse mammary gland end buds cultured in a collagen gel matrix. Exp Cell Res 141: 433–443

    Google Scholar 

  • Richards J, Yang J, Guzman R, Pasco D, Nandi S (1982b) Effects of a collagen gel matrix on the growth of cultured mouse mammary cells. In: Hawkes S, Wang JL (eds) Academic Press, New York (Extracellular Matrix, p 315)

    Google Scholar 

  • Shafie SM (1980) Estrogen and the growth of breast cancer: new evidence suggets indirect action. Science 209: 701–702

    Google Scholar 

  • Siiteri P (1978) Steroid hormones and endometrial cancer. Cancer Res 38: 4360–4366

    Google Scholar 

  • Sirbasku DA (1978) Estrogen induction of growth factors specific for hormone-responsive mammary, pituitary and kidney tumor cells. Proc Natl Acad Sci USA 75: 3786–3790

    Google Scholar 

  • Sirbasku DA, Benson RH (1979) Estrogen-inducible growth factors that may act as mediators (estromedins) of estrogen-promoted tumor cell growth. Cold Spring Harbor Conf Cell Prolif 6: 477–497

    Google Scholar 

  • Sirbasku DA, Leland FE (1982) Estrogen-inducible growth factors:proposal of new mechanisms of estrogen-promoted tumor cell growth. In: Litwack A (ed) Academic Press, New York (Biochemical Actions of Hormones, Vol 9, p 115)

    Google Scholar 

  • Smith DC, Prentice RL, Bauermeister DE (1981) Endometrial Carcinoma: Histopathology, survival and exogenous estrogen. Gynecol Obstet Invest 12: 169–179

    Google Scholar 

  • Sutherland RL, Reddel RR, Green MD (1983) Effects of oestrogens on cell proliferation and cell cycle kinetics. A hypothesis on the cell cycle effects of antiestrogens. Eur J Cancer Clin Oncol 19: 307–318

    Google Scholar 

  • Thomas DB (1978) Role of exogenous female hormones in altering the risk of benign and malignant neoplasms in humans. Cancer Res 38: 3991–4000

    Google Scholar 

  • Tomooka Y, Larson L, Imagawa W (1983) Mitogenic effects of hormones on mouse mammary epithelial cells in serum-free collagen gel culture. Breast Cancer Research Conf: Proc of Int Symp held in Denver, CO March 20–24, p 35

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

    Google Scholar 

  • Yang J, Nandi S (1983) Growth of cultured cells using collagen as substrate. Int Rev Cytol 81: 249–286

    Google Scholar 

  • Yang J, Richards J, Bowman P, Guzman R, Enami J, McCormick K, Hamamoto S, Pitelka D, Nandi S (1979) Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gels. Proc Natl Acad Sci USA 76: 3401–3405

    Google Scholar 

  • Yang J, Richards J, Guzman R, Imagawa W, Nandi S (1980a) Sustained growth in primary culture of normal mammary epithelial cells embedded in collagen gels. Proc Natl Acad Sci USA 77: 2088–2092

    Google Scholar 

  • Yang J, Guzman R, Richards J, Imagawa W, McCormick K, Nandi S (1980b) Growth factor- and cyclic nucleotide-induced proliferation of normal and malignant mammary epithelial cells in primary culture. Endocrinol 107: 35–41

    Google Scholar 

  • Zummoff B (1981) The role of endogenous estrogen excess in human breast cancer (Review). Anticancer Res 1: 39–44

    Google Scholar 

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Authors and Affiliations

  1. Department of Zoology and Cancer Research Laboratory, University of California, 94720, Berkeley, California, USA

    Satyabrata Nandi, Walter Imagawa, Yasuhiro Tomooka, Michael F. McGrath & Marc Edery

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  1. Satyabrata Nandi
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  2. Walter Imagawa
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  3. Yasuhiro Tomooka
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  4. Michael F. McGrath
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  5. Marc Edery
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Additional information

Preparation of this brief review was aided by grants CA05388 and CA09041 from NIH, DHHS

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Nandi, S., Imagawa, W., Tomooka, Y. et al. Collagen gel culture system and analysis of estrogen effects on mammary carcinogenesis. Arch Toxicol 55, 91–96 (1984). https://doi.org/10.1007/BF00346045

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  • DOI: https://doi.org/10.1007/BF00346045

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