Pathogenesis of Ductal and Lobular Progestin-Induced Mammary Carcinomas in BALB/c Mice
Several years ago, we demonstrated that medroxyprogesterone acetate (MPA)- induced mammary adenocarcinomas in female BALB/c mice with an incidence close to 80% and a mean latency of around 13 months (1). These tumors were mostly ductal, progestin-dependent (PD) adenocarcinomas with high levels of estrogen and progesterone receptors (ER and PR) (2). We later found that progesterone (P) also induced mammary carcinomas, but this time the tumors were mostly lobular, progestin-independent (PI) adenocarcinomas with lower levels of ER and PR (3). There was a constant correlation between progestin dependence and morphology, that is, lobular carcinomas were always PI and ductal carcinomas PD (3). To extend this study further, we designed a model of co-carcinogenesis using medroxyprogesterone (MPA) with N-methyl N-nitrosourea (MNU) in BALB/c mice. We obtained a high incidence of mammary adenocarcinomas similar to the hormone-induced lobular tumors, and showed that MPA can act as a potent promoter.
KeywordsSalivary Gland Mammary Gland Mammary Tumor Mammary Carcinoma Tumor Line
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Lanari C, Molinolo AA, Dosne Pasqualini C (1986) Induction of mammary adenocarcinomas by medroxyprogesterone acetate in BALB/c female mice. Cancer Lett 33:215–223.PubMedCrossRefGoogle Scholar
Molinolo AA, Lanari C, Charreau EH (1987) Mouse mammary tumors induced by medroxyprogesterone acetate: Immunohistochemistry and hormonal receptors. J Natl Cancer Inst 79:1341–1350.PubMedGoogle Scholar
Kordon E, Molinolo A A, Pasqualini CD (1993) Progesterone induction of mammary carcinomas in BALB/c female mice. Correlation between hormone dependence and morphology. Breast Cancer Res Treat 28:29–39.PubMedCrossRefGoogle Scholar
Stoschek CM, King LE (1986) Role of epidermal growth factor in carcinogenesis. Cancer Res 46:1030–1037.Google Scholar
Bullock LP, Barthe TH, Mawzowicz ICW (1975) The effect of progestin on submaxillary gland epidermal growth factor: Demonstration of androgenic, synandrogenic and anti-androgenic actions. Endocrinology 97:189–195.PubMedCrossRefGoogle Scholar
Perheentupa J, Lakshmanan J, Hoath SB, Fisher DA (1984) Hormonal modulation of plasma concentration of epidermal growth factor. Acta Endocrinol 107:571–576.PubMedGoogle Scholar
Kurachi H, Okamoto S, Oka T (1985) Evidence for the involvement of the submandibular gland epidermal growth factor in mouse mammary tumorigenesis. Proc Natl Acad Sci USA 82:5940–5943PubMedCrossRefGoogle Scholar
Inui T, Tsubura A, Morii S (1989) Incidence of precancerous foci of mammary glands and growth rate of transplantable mammary cancers in s ialoadenectomized mice. J Natl Cancer Inst 81:1660–1663.PubMedCrossRefGoogle Scholar
© Springer-Verlag New York, Inc. 1996