Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate

Li, Shengmin; Lepage, Martin; Mérand, Yves; Bélanger, Alain; Labrie, Fernand

doi:10.1007/bf01961245

Cited by 12 publications

(4 citation statements)

References 36 publications

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“…It should be mentioned that in vivo studies have demonstrated that controlled release of low-dose MPA, a compound having androgenic activity, also exerts a potent inhibitory effect on the development and growth of DMBA-induced mammary carcinoma in the rat (243,244). MPA has in fact been clearly shown to exert androgenic inhibitory effects on the growth of human breast cancer cells in vitro (209, 231, (246,247).…”

Section: B Preclinical Datamentioning

confidence: 97%

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

et al. 2003

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Serum androgens as well as their precursors and metabolites decrease from the age of 30-40 yr in women, thus suggesting that a more physiological hormone replacement therapy at menopause should contain an androgenic compound. It is important to consider, however, that most of the androgens in women, especially after menopause, are synthesized in peripheral intracrine tissues from the inactive precursors dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) of adrenal origin. Much progress in this new area of endocrine physiology called intracrinology has followed the cloning and characterization of most of the enzymes responsible for the transformation of DHEA and DHEA-S into androgens and estrogens in peripheral target tissues, where the locally produced sex steroids are exerting their action in the same cells in which their synthesis takes place without significant diffusion into the circulation, thus seriously limiting the interpretation of serum levels of active sex steroids. The sex steroids made in peripheral tissues are then inactivated locally into more water-soluble compounds that diffuse into the general circulation where they can be measured. In a series of animal models, androgens and DHEA have been found to inhibit breast cancer development and growth and to stimulate bone formation. In clinical studies, DHEA has been found to increase bone mineral density and to stimulate vaginal maturation without affecting the endometrium, while improving well-being and libido with no significant side effects. The advantage of DHEA over other androgenic compounds is that DHEA, at physiological doses, is converted into androgens and/or estrogens only in the specific intracrine target tissues that possess the appropriate physiological enzymatic machinery, thus limiting the action of the sex steroids to those tissues possessing the tissue-specific profile of expression of the genes responsible for their formation, while leaving the other tissues unaffected and thus minimizing the potential side effects observed with androgens or estrogens administered systemically.

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Section: B Preclinical Datamentioning

confidence: 97%

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

et al. 2003

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“…Long-term in vivo studies of progesterone effects in tumor models are sparse. Progesterone treatment inhibits proliferation of established rat mammary tumors (19,20) and PR-transfected MDA-231 (ERÀPRÀ) human breast cancer cells grown into tumors in severe combined immunodeficient mice (21). On the other hand, Michna et al (22) report inhibitory effects of antiprogestins, in which case progesterone would be growth stimulatory.…”

Section: Introductionmentioning

confidence: 99%

Progestins Initiate a Luminal to Myoepithelial Switch in Estrogen-Dependent Human Breast Tumors without Altering Growth

Sartorius¹,

Harvell²,

Shen³

et al. 2005

Cancer Research

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Although long-term clinical use of progestins is associated with an increased incidence of breast cancers, their role in established cancers is unclear. Estrogens are considered to be the main mitogens in the majority of breast cancers. Whether progesterone affects proliferation and/or differentiation is under debate. To assess the role of progesterone in established breast cancers, we used T47D human breast cancer cells that are estrogen receptor (ER) positive and either progesterone receptor (PR) negative or positive for PRA, PRB, or both. These cells were grown as strictly estrogen-dependent solid tumors in ovariectomized female nude mice. Progesterone or medroxyprogesterone acetate (MPA) alone did not support tumor growth, nor did progesterone or MPA given simultaneously with estrogen significantly alter estrogen-dependent tumor growth. However, treatment of mice bearing ER+PR+ but not ER+PRÀ tumors with either progesterone or MPA increased expression of the myoepithelial cytokeratins (CK) 5 and 6 in a subpopulation of tumor cells. These CK5+/CK6+ cells had decreased expression of luminal epithelial CK8, CK18, and CK19. We conclude that progestins exert differentiative effects on tumors characterized by transition of a cell subpopulation from luminal to myoepithelial. This may not be beneficial, however, because such a phenotype is associated with poor prognosis. (Cancer Res 2005; 65(21): 9779-88)

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“…As mentioned earlier, MPA has been shown to exert a direct inhibition of the proliferation of ZR-75-1 human breast cancer cells in vitro (Poulin et al, 1989a). An androgen receptor-mediated direct anti-proliferation mechanism (Labrie et al, 1993;Li et al, 1992) as well as an inhibition of the intracellular formation of the active estrogen estradiol by inhibiting 17␤-hydroxysteroid dehydrogenase (17␤-HSD) have been suggested to explain the anti-tumoral effect of MPA in DMBA-induced rat mammary carcinoma (Li et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of the novel anti-estrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthracene-induced mammary carcinoma in rats

Luo¹,

Stojanović²,

Labrie³

et al. 1997

Int. J. Cancer

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Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate

Cited by 12 publications

References 36 publications

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

Progestins Initiate a Luminal to Myoepithelial Switch in Estrogen-Dependent Human Breast Tumors without Altering Growth

Inhibitory effect of the novel anti-estrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthracene-induced mammary carcinoma in rats

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