Association of estrogen receptor-α and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment

Girard, Guadalupe Montero; Vanzulli, Silvia I.; Cerliani, Juan P.; Bottino, María Cecilia; Bolado, Julieta; Vela, Jorge Espino; Becú-Villalobos, Damasia; Benavides, Fernando; Gutkind, J. Silvio; Patel, Vyomesh; Molinolo, Alfredo A.; Lanari, Claudia

doi:10.1186/bcr1660

Cited by 21 publications

(17 citation statements)

References 60 publications

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“…However, there is to our knowledge no study regarding antiprogestin-resistance in breast cancer. The main reason is that despite all the increasing evidence relating PR with proliferative signals in the mammary gland [4,6,46], there are very few studies focused on unraveling the role of PR in breast cancer.…”

Section: Discussionmentioning

confidence: 97%

“…Progesterone has been shown to be required for the proliferation of mammary glands [4][5][6] and mammary carcinomas [7,8]. The synthetic progesterone, medroxyprogesterone acetate (MPA) behaves experimentally as a mammary-specific carcinogen [9][10][11], and most importantly, in combination with E 2 , it is associated with an increased risk of breast cancer development [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas

Wargon

Helguero

Bolado

et al. 2008

Breast Cancer Res Treat

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To explore mechanisms related to hormone resistance, three resistant variants of the MPA mouse breast cancer tumor model with low levels of progesterone receptor (PR) isoform A (PR-A)/high PR-B expression were developed by prolonged selective pressure with antiprogestins. The resistant phenotype of one tumor line was reversed spontaneously after several consecutive passages in syngeneic BALB/c mice or by 17-beta-estradiol or tamoxifen treatment, and this reversion was significantly associated with an increase in PR-A expression. The responsive parental tumors disclosed low activation of ERK and high activation of AKT; resistant tumors on the other hand, showed the opposite, and this was associated with a higher metastatic potential, that did not revert. This study shows for the first time in vivo a relationship between PR isoform expression and antiprogestin responsiveness, demonstrating that, whereas acquired resistance may be reversed, changes in kinase activation and metastatic potential are unidirectional associated with tumor progression.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas

Wargon

Helguero

Bolado

et al. 2008

Breast Cancer Res Treat

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“…Like the uterus (5), phenotypic variation in the responsiveness of the adult mammary gland to E 2 , during both normal and pathological conditions, including tumor formation, was reported long ago (6, 16, 17). In addition, genetic control of mammary development (18), response to hormones (19), and ductal morphology (20, 27) have been observed. Blair et al (17) observed marked variation in mammary alveolar development induced by treatment with E 2 and progesterone in several strains of male mice, including B6 and C3H.…”

Section: Mammary Glandmentioning

confidence: 99%

“…Therefore, many of the studies investigating the strain differences in the response of the mammary gland to E 2 that were published before 1999 were either confounded by the presence of MMTV or were designed to investigate the mammary response to E 2 in the context of MMTV (7,16,17,(22)(23)(24)(25)(26). More recent reports have confirmed that, even in the absence of MMTV, the response of the mammary gland to E 2 and progesterone (19) and to environmental estrogens (27,28) is genetically controlled.…”

Section: Mammary Glandmentioning

confidence: 99%

The role of genetics in estrogen responses: a critical piece of an intricate puzzle

et al. 2014

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The estrogens are female sex hormones that are involved in a variety of physiological processes, including reproductive development and function, wound healing, and bone growth. They are mainly known for their roles in reproductive tissues-specifically, 17␤-estradiol (E 2 ), the primary estrogen, which is secreted by the ovaries and induces cellular proliferation and growth of the uterus and mammary glands. In addition to the role of estrogens in promoting tissue growth and development during normal physiological states, they have a well-established role in determining susceptibility to disease, particularly cancer, in reproductive tissues. The responsiveness of various tissues to estrogen is genetically controlled, with marked quantitative variation observed across multiple species, including humans. This variation presents both researchers and clinicians with a veritable physiological puzzle, the pieces of which-many of them unknown-are complex and difficult to fit together. Although genetics is known to play a major role in determining sensitivity to estrogens, there are other factors, including parent of origin and the maternal environment, that are intimately linked to heritable phenotypes but do not represent genotype, per se. The objectives of this review article were to summarize the current knowledge of the role of genotype, and uterine and neonatal environments, in phenotypic variation in the response to estrogens; to discuss recent findings and the potential mechanisms involved; and to highlight exciting research opportunities for the future.

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“…In this report, we validated the effectiveness of our HMSP by comparing the effect on HD and HI tumor growth with commercially available sc MPA pellets or daily injections of MFP solution, that have proven to be effective in inducing or inhibiting tumor growth, respectively [13]. Pg HMSP induced lobular differentiation in mammary glands from ovariectomized mice [30], [31]. We found that HMSP induced similar biological effects on tumor growth and mammary gland histology as the other validated methods used to administer steroids, demonstrating that this is an effective method for delivering steroids to mice.…”

Section: Discussionmentioning

confidence: 91%

Novel, Low Cost, Highly Effective, Handmade Steroid Pellets for Experimental Studies

et al. 2013

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The basic component of Silastic® glue (Dow Corning) used to prepare Silastic® pellets is polydimethylsiloxane. This compound is also present in other commercial adhesives such as FASTIX® (Akapol SA) that are available in any store for that category. In the present study we developed low cost, easy to prepare handmade steroid pellets (HMSP) by mixing 17β-estradiol, progesterone or other synthetic steroids with FASTIX® adhesive. We assessed serum levels of 17β-estradiol, progesterone, prolactin and luteinizing hormone in ovariectomized mice treated for 24 and 48 h or 7, 14 and 28 days with 20 µg or 5 mg of 17β-estradiol or 5 mg progesterone HMSP. We found a time dependent and significant increase in the levels of both natural hormones, and a downregulation of serum luteinizing hormone levels, while both 17β-estradiol doses increased serum prolactin. Uterine weights at sacrifice and histological examination of the uteri and the mammary glands correlated with estrogen or progestin action. Finally, we evaluated the biological effects of HMSP compared to commercial pellets or daily injections in the stimulation or inhibition of hormone dependent mammary tumor growth, and found that HMSP were as effective as the other methods of hormone administration. These data show that HMSP represent a useful, low cost, easily accessible method for administering steroids to mice.

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Association of estrogen receptor-α and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment

Cited by 21 publications

References 60 publications

Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas

Reversal of antiprogestin resistance and progesterone receptor isoform ratio in acquired resistant mammary carcinomas

The role of genetics in estrogen responses: a critical piece of an intricate puzzle

Novel, Low Cost, Highly Effective, Handmade Steroid Pellets for Experimental Studies

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