Medroxyprogesterone acetate enhances spontaneous mammary tumorigenesis and uterine adenomyosis in mice

Nagasawa, Hiroshi; Aoki, Makoto; Sakagami, Nobutada; Ishida, Masahiro

doi:10.1007/bf01805741

Cited by 27 publications

(14 citation statements)

References 13 publications

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“…In another strain of mice, in MPA-treated C3H virgin females, an increase in mammary tumor incidence was also observed [4]. In a recent paper, Nagasawa et al [5] also demonstrated that MPA increased mamma D' tumor incidence in SHN mice. This tumorigenic effect of MPA on mammary glands had already been described in beagle dogs many years ago [6,7].…”

Section: Introductionmentioning

confidence: 80%

Mammary carcinogenesis induced byN-methyl-N-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) inBALB/c mice

Pazos

Lanari

Meiss

et al. 1991

Breast Cancer Res Tr

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MPA induces mammary tumors in virgin BALB/c mice with an average latency of 52 weeks. In order to determine whether the simultaneous administration of a chemical carcinogen, N-methyl-N-nitrosourea (MNU), shortened the latency of MPA-induced tumors, a total of 60 virgin female BALB/c mice were treated with either MNU + MPA or MNU or MPA. The experiment lasted 7 months. The incidence and latency of mammary tumors were significantly different between the 3 groups: 15/19 (79%) in MNU + MPA-treated mice with a latency of 154 +/- 19 days; 3/20 (15%) in MNU-treated mice with a latency of 179 +/- 7 days; 0/20 (tumors only start appearing after 10 months) in MPA-treated mice. Histologically, MNU + MPA-induced tumors were similar to the few tumors observed in MNU-treated mice: most of them were type B adenocarcinomas with a high degree of necrosis and calcification. Only one of the MNU + MPA-induced tumors expressed high levels of ER and PR and proved to be MPA-responsive in further passages. All the other tumors showed low or non-detectable levels of ER and PR together with an independent pattern of tumor growth. In MNU-treated mice the only tumor that was transplanted proved to be hormone independent and had low levels of PR and ER. In both MNU and MNU + MPA treated mice lung adenocarcinomas were detected. Cystic uterine glandular hyperplasias were observed in all animals. It can be concluded that MPA and MNU potentiate their carcinogenic effect in mammary gland.

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Section: Introductionmentioning

confidence: 80%

Mammary carcinogenesis induced byN-methyl-N-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) inBALB/c mice

Pazos

Lanari

Meiss

et al. 1991

Breast Cancer Res Tr

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“…Progesterone also has been implicated in the growth of carcinogen-induced (Welsch 1985) and transplantable rat mammary tumors (Robinson and Jordan 1987) as well as in spontaneous tumorigenesis of the murine mammary gland (Nagasawa et al 1988). As further support for the stimulatory effect of progestins on the mammary gland epithelium, antiprogestins were found to inhibit the growth effects of progesterone in certain experimental mammary tumors, suggesting that the proliferative actions of progesterone are mediated through the PR (Michna et al 1989).…”

Section: Mammary Gland Lobuloalveolar Development Requires Prmentioning

confidence: 99%

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Lydon¹,

DeMayo²,

Funk³

et al. 1995

Genes Dev.

1,703

1,242

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Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.

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“…Progestins increase the incidence of spontaneous mammary tumors in dogs (Frank et al, 1979) and mice (Nagasawa et al, 1988). We found that progesterone can promote DMBA-induced mammary carcinogenesis in rats (Wiehle et al, 2007).…”

Section: Prms In In Vivo Experimental Modelsmentioning

confidence: 59%

Progesterone receptor modulators in breast cancer

Wiehle¹,

2014

Turk J Biol

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Breast cancer has been treated successfully with selective estrogen receptor antagonists (SERMs) such as tamoxifen, receptordepleting agents such as fulvestrant, and aromatase inhibitors such as anastrozole. Selective progesterone receptor modulators (SPRMs or PRMs) have not been studied as much and are currently under investigation for inhibition of mammary carcinogenesis in animal models and breast cancer prevention trials in women. They might follow tamoxifen and aromatase inhibitors in the adjuvant treatment of breast cancers with acquired resistance. These uses have not provoked ground-breaking progress or studies and PRMs do not have a high profile. Most in vitro and in vivo studies indicate that PRMs preferentially suppress cell proliferation and also induce apoptosis. In this review we summarized the data on the effects of PRMs and particularly of the antiprogestins RU-486 (mifepristone) and CDB-4124 (Progenta, Proellex or telapristone acetate) on breast cancer models. Both agents have been employed in preclinical and clinical studies for prevention and treatment of breast cancer. This author believes that PRMs should be investigated more intensely.

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Medroxyprogesterone acetate enhances spontaneous mammary tumorigenesis and uterine adenomyosis in mice

Cited by 27 publications

References 13 publications

Mammary carcinogenesis induced byN-methyl-N-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) inBALB/c mice

Mammary carcinogenesis induced byN-methyl-N-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) inBALB/c mice

Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

Progesterone receptor modulators in breast cancer

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