Summary
The administration of MPA to virgin female BALB/c mice led to the development of mammary adenocarcinomas, which in furtherin vivo transplants gave rise to both MPA-dependent and MPA-independent lines. In this paper we chose one of the MPA-dependent lines with high contents of estrogen (ER) and progesterone (PR) receptors, and were able to demonstrate that a) the growth of these tumors could be manipulated by the administration or the withdrawal of the hormonal supply;b) PR were down-regulated in MPA-treated mice; c) progesterone had the same stimulatory effect as MPA on tumor growth; d) tumors did not grow in estrogen-treated mice; e) tumor growth was much lower in males than in females; f) the presence of the ovaries had a positive influence on tumor growth, even in the presence of MPA; g) the withdrawal of progestin pellets in ovariectomized mice usually led to complete remissions followed by regrowth of the tumors after several weeks; and h) the regrowing tumors maintained their steroid receptor pattern and (in 3 out of 4 cases) their hormone-dependent behavior in further passages.
Abbreviations
- DMBA:
-
7,12 dimethylbenz(a)anthracene
- EB:
-
estradiol benzoate
- ER:
-
estrogen receptors
- MPA:
-
medroxyprogesterone acetate
- P:
-
progesterone
- PR:
-
progesterone receptors
References
Bonte J: Hormone dependency and hormone responsiveness of endometrial adenocarcinoma to estrogens, progestagens and antiestrogens. In: Campio L, Robustelli Della Cuna G, Taylor RW (eds) Role of Medroxyprogesterone in Endocrine-Related Tumors, Vol. 2. Raven Press, New York, 1983, pp 141–156
Taylor RW: The treatment of endometrial carcinoma with medroxyprogesterone acetate. In: Campio L, Robustelli Della Cuna G, Taylor RW (eds) Role of Medroxyprogesterone in Endocrine-Related Tumors, Vol. 2. Raven Press, New York, 1983, pp 157–162
Cavalli F, Goldhirsch A, Jungi F, Martz G, Alberto P: Low-versus high-dose medroxyprogesterone acetate in the treatment of advanced breast cancer. In: Campio L, Robustelli Della Cuna G, Taylor RW (eds) Role of Medroxyprogesterone in Endocrine-Related Tumors, Vol. 2. Raven Press, New York, 1983, pp 69–75
Pannuti F, Camaggi CM, Strocchi E, Giovannini M, Iafelice G, Canova N, Costanti B, Murari G: High-dose medroxyprogesterone acetate therapy: Plasma levels and bioavailability-response correlation after single and multiple dose administration in advanced cancer patients. Preliminary results. In: Campio L, Robustelli Della Cuna G, Taylor RW (eds) Role of Medroxyprogesterone in Endocrine-Related Tumors, Vol. 2. Raven Press, New York, 1983, pp 35–42
Pellegrini A, Massidda B, Mascia V, Lippi MG, Ionta MT, Muggiano A, Carboni-Boi E: Aspects of the rationale to hormono and hormono-chemotherapy in advanced breast cancer. In: Iacobelli S, Di Marco A (eds) Role of Medroxyprogesterone in Endocrine-Related Tumors. Raven Press, New York, 1980, pp 29–39
Pike MC, Henderson BE, Casagrande JT, Rosario I, Cray GE: Oral contraceptive use and early abortion as risk factors for breast cancer in young women. Br J Cancer 43: 72–76, 1981
Pike MC, Henderson BE, Krailo MD, Duke A, Roy S: Breast cancer in young women and use of oral contraceptives: possible modifying effect of formulation and age at use. Lancet ii: 926–930, 1983
WHO Collaborative Study of Neoplasia and Steroid Contraceptives: Breast cancer, cervical cancer, and depot medroxyprogesterone acetate. Lancet ii: 1207–1208, 1984
Concannon P, Altszuler N, Hampshire J, Butler WR, Hansel W: Growth hormone, prolactin and cortisol in dogs developing mammary nodules and acromegaly-like appearance ance during treatment with medroxyprogesterone acetate. Endocrinology 106: 1173–1177, 1980
Frank DW, Kirton KT, Murchison TE, Quiplan WJ, Coleman TJ, Gilbertson TJ, Feenstra ES, Kimball FA: Mammary tumors and serum hormones in the bitch treated with medroxyprogesterone acetate and progesterone for four years. Fertil Steril 31: 340, 1979
Sun M: Panel says Depo-Provera not proved safe. Science 226: 950–951, 1984
Danguy A, Legros N, Devleeschouwer N, Heuson-Stennon JA, Heuson JC: Effects of medroxyprogesterone acetate (MPA) on growth of DMBA-induced rat mammary tumors: Histopathological and endocrine studies. In: Iacobelli S, Di Marco A (eds) Role of Medroxyprogesterone in Endocrine-Related Tumors. Raven Press, New York, 1980, pp 21–28
Russo IH, Gimotty P, Dupuis M, Russo J: Effect of medroxyprogesterone acetate on the response of the rat mammary gland to carcinogenesis. Br J Cancer 59: 210–216, 1989
Nagasawa H, Aoki M, Sakagami N, Ishida M: Medroxy-progesterone acetate enhances spontaneous mammary tumorigenesis and uterine adenomyosis in mice. Breast Cancer Res Treat 12: 59–66, 1988
Lanari C, Kordon E, Molinolo AA, Charreau EH, Dosne Pasqualini C: Inducción de adenocarcinomas de mama por acetato de medroxiprogesterona en ratones hembras C3H. Medicina 47: 652–653, 1987
Lanari C, Molinolo AA, Dosne Pasqualini C: Induction of mammary adenocarcinomas by medroxyprogesterone acetate in BALB/c female mice. Cancer Lett 33: 215–223, 1986
Lanari C, Kordon E, Molinolo A, Dosne Pasqualini C, Charreau EH: Mammary adenocarcinomas induced by medroxyprogesterone acetate: Hormone dependence and EGF receptors of BALB/cin vivo sublines. Int J Cancer 43: 845–850, 1989
Bullock LP, Barthe TL, Mawsowicz I, North A, Bardin CW: The effects of progestins on submaxillary gland epidermal growth factor: Demonstration of androgenic, synandrogenic, and anti-androgenic actions. Endocrinology 97: 189–195, 1975
El Etreby MF, Graf KJ, Gunzel P, Neumann F: Evaluation of effects of sexual steroids on the hypothalamic-pituitary systems of animals and man. Arch Toxicol, Suppl 2: 11–39, 1979
Calandra RS, Charreau EH, Royer de Giaroli M, Baldi A, Calvo JC, Pujato D, Arrighi L: Receptores para esteroides y prolactina en carcinomas mamarios humanos. Medicina (Bs. Aires) 40: 718–725, 1980
Korenman SG, Dukes BA: Specific estrogen binding by the cytoplasm of human breast carcinoma. J Clin Endocr Metab 30: 639–645, 1970
Molinolo AA, Lanari C, Charreau EH, Sanjuan N, Dosne Pasqualini C: Mouse mammary tumors induced by medroxyprogesterone acetate: immunohistochemistry and hormonal receptors. J Natl Cancer Inst 79: 1341–1350, 1987
Saas B, Dunn TB: Classification of mouse mammary tumors in Dunn's miscellaneous group including recent reported types. J Natl Cancer Inst 62: 1287–1293, 1979
Satyaswaroop PG, Sivarajah A, Zaino RJ, Mortel R: Hormonal control of growth of human endometrial carcinoma in the nude mouse model. In: Bresciani F, King RJB, Lippman ME, Raynaud JP (eds) Hormones and Cancer, 3. Raven Press, New York, 1988, pp 430–435
Zaccheo T, Di Salle F: Experimental antitumor activity of medroxyprogesterone acetate. In: Robustelli Della Cuna G, Tepmongkol P, Somboonchareon S (eds) The Role of High Dose Medroxyprogesterone Acetate in the Management of Endocrine-Related Tumors. Bangkok, Thailand, 1985, pp 3–20
Robustelli Della Cuna G, Preti P: Advanced breast cancer: Hormone-dependency and mechanisms of action of medroxyprogesterone acetate. In: Robustelli Della Cuna G, Tepmongkol P, Somboonchareon S (eds) The Role of High Dose Medroxyprogesterone Acetate in the Management of Endocrine-Related Tumors. Bangkok, Thailand, 1985, pp 21–27
Schneider M, Michna H, Nishino Y, Fathy El Etreby M: Anti-tumor activity of the progesterone antagonists ZK 98.299 and RU 38.486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA-and the MNU-induced mammary tumor models of the rat. Eur J Cancer Clin Oncol 25: 691–701, 1989
Russo J, Tay LK, Russo IH: Differentiation of the mammary gland and suceptibility to carcinogenesis. Breast Cancer Res Treat 2: 5–73, 1982
De Launoit Y, Kiss R, Danguy A, Paridaens R: Effect of ovariectomy, hypophysectomy and/or GnRH analog (HRF) administration on the cell proliferation of the MXT mouse hormone-dependent mammary tumor. Eur J Cancer Clin Oncol 23: 1443–1450, 1987
Matsuzawa A, Yamamoto T: Response of a pregnancydependent mouse mammary tumor to hormones. J Natl Cancer Inst 55: 447–453, 1975
Welsch CW, Nagasawa H: Prolactin and murine mammary tumorigenesis: a review. Cancer Res 37: 951–963, 1977
Nagasawa H, Fujii M, Hagiwara K: Inhibition by medroxyprogesterone acetate of precancerous mammary hyperplastic alveolar nodule formation in mice. Breast Cancer Res Treast 5: 31–36, 1985
Lanari C, Molinolo AA, Dosne Pasqualini C: Inhibitory effect of medroxyprogesterone acetate on foreign body tumorigenesis in mice. JNCI 77: 157–164, 1986
Keski-Oja J, Leof EB, Lyons RM, Coffey RJ Jr, Moses HL: Transforming growth factors and control of neoplastic cell growth. J Cell Biochem 33: 95–107, 1987
Sluyser M, Van Nie R: Estrogen receptor content and hormone responsive growth of mouse mammary tumors. Cancer Res 34: 3253–3257, 1974
Labrie F, Veilleux R, Fournier A: Low androgen levels induce the development of androgen-hypersensitive cell clones in Shionogi mouse mammary carcinoma cells in culture. J Natl Cancer Inst 80: 1138–1147, 1988
Bélanger A, Le Goff JM, Prouix L, Caron S, Labrie F: Presence of C-19 steroids in mammary Shionogi carcinoma (SC 115) in castrated mice. Cancer Res 45: 6293–6295, 1985
Spinola PG, Marchetti B, Labrie F: Adrenal steroids stimulate growth and progesterone receptor levels in rat uterus and DMBA-induced mammary tumors. Breast Cancer Res Treat 8: 241–248, 1986
Darbre P, King RJ: Progression to steroid insensitivity can occur irrespective of the presence of functional steroid receptors. Cell 51: 521–528, 1987
Bardin CW: The androgenic, antiandrogenic, and synandrogenic actions of progestins. In: Bardin CW, Milgrom E, Mauvais-Jarvis P (eds): Progesterone and Progestins. Raven Press, New York, 1983
Kurachi H, Okamoto S, Oka T: Evidence for the involvement of the submandibular gland epidermal growth factor in mouse mammary tumorigenesis. Proc Natl Acad Sci USA 82: 5940–5943, 1985
Inui T, Tsubura A, Morii S: Incidence of precancerous foci of mammary glands and growth rate of transplantable mammary cancers in sialoadenectomized mice. J Natl Cancer Inst 81: 1660–1663, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kordon, E., Lanari, C., Meiss, R. et al. Hormone dependence of a mouse mammary tumor line inducedin vivo by medroxyprogesterone acetate. Breast Cancer Res Tr 17, 33–43 (1990). https://doi.org/10.1007/BF01812682
Issue Date:
DOI: https://doi.org/10.1007/BF01812682