Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

Yun, Bo Hyon; Seong, Seok Ju; Hyun, Dong Choon; Kim, Ji Yeon; Kim, Miseon; Shim, Jae‐Yong; Park, Ji Eun

doi:10.1016/j.ejogrb.2015.05.022

Cited by 18 publications

(13 citation statements)

References 28 publications

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“…However, UPA treatment did not change Bcl-2 protein expression in myomas, even after repeated intermittent UPA courses. These findings corroborate in vivo studies into uterine myomas after 3 months of UPA treatment, revealing no Bcl-2 repression [66, 67] but do not confirm in vitro data showing that UPA and another similar SPRM repress Bcl-2 protein expression in myoma cell culture [26, 68]. The methodology applied and timing of treatment may explain the discrepancy between in vitro and in vivo observations.…”

Section: Discussionsupporting

confidence: 73%

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Courtoy

Donnez

Marbaix

et al. 2017

Gynecol Obstet Invest

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Objective: To investigate whether ulipristal acetate (UPA) treatment modifies the expression of progesterone receptor (PR), its nuclear cofactors steroid receptor coactivator-1 (SRC1) and nuclear corepressor-1 (NCoR1), prosurvival factor B-cell lymphoma 2 (Bcl-2), and Akt in uterine myomas. Patients: Prospective study of 59 women with symptomatic myomas undergoing myomectomy. Forty-two patients were treated preoperatively with UPA; the remaining 17 were not and they served as controls. Method: Tissue microarrays were obtained from surgical specimens and immunohistochemistry was performed. Blinded quantification of expression of PR (PR-A vs. PR-B), coactivator SRC1 and corepressor NCoR1, and prosurvival factor Bcl-2, and Akt and evaluation of Akt phosphorylation levels. Results: Compared with the control group, UPA does not alter PR protein levels or expression patterns in myomas, and the PR-A/PR-B ratio was similar, as well as cytoplasmic or nuclear expression of cofactors SRC1 and NCoR1. Bcl-2 was heterogeneously expressed throughout the samples and no significant modification in expression was evidenced. No significant difference was found in Akt expression and phosphorylation between treated and untreated myomas. Conclusion: This study did not find any significant change in the expression of the studied factors in myomas after UPA exposure. In conclusion, various theories on myomas cells proposed on the basis of in vitro studies are not supported in vivo.

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Section: Discussionsupporting

confidence: 73%

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Courtoy

Donnez

Marbaix

et al. 2017

Gynecol Obstet Invest

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“…Ulipristal acetate is a recently released selective progesterone receptor modulator routinely used for emergency contraception [ 21 ] and mid to long term leiomyoma treatment [ 22 – 23 ]. This compound exerts mixed agonist/antagonist activities depending on the cellular context and has been shown to induce apoptosis in cultured leiomyoma cells [ 24 ] and in leiomyoma in vivo [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Ulipristal Acetate Inhibits Progesterone Receptor Isoform A-Mediated Human Breast Cancer Proliferation and BCl2-L1 Expression

et al. 2015

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The progesterone receptor (PR) with its isoforms and ligands are involved in breast tumorigenesis and prognosis. We aimed at analyzing the respective contribution of PR isoforms, PRA and PRB, in breast cancer cell proliferation in a new estrogen-independent cell based-model, allowing independent PR isoforms analysis. We used the bi-inducible human breast cancer cell system MDA-iPRAB. We studied the effects and molecular mechanisms of action of progesterone (P4) and ulipristal acetate (UPA), a new selective progesterone receptor modulator, alone or in combination. P4 significantly stimulated MDA-iPRA expressing cells proliferation. This was associated with P4-stimulated expression of the anti-apoptotic factor BCL2-L1 and enhanced recruitment of PRA, SRC-1 and RNA Pol II onto the +58 kb PR binding motif of the BCL 2 -L 1 gene. UPA decreased cell proliferation and repressed BCL2-L1 expression in the presence of PRA, correlating with PRA and SRC1 but not RNA Pol II recruitment. These results bring new information on the mechanism of action of PR ligands in controlling breast cancer cell proliferation through PRA in an estrogen independent model. Evaluation of PR isoforms ratio, as well as molecular signature studies based on PRA target genes could be proposed to facilitate personalized breast cancer therapy. In this context, UPA could be of interest in endocrine therapy. Further confirmation in the clinical setting is required.

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“…It has been known that uterine leiomyomas are a hormonedependent disease. However, the mechanism of action is still unknown, and there is increasing evidence that steroid hormones, estrogen and progesterone receptors are not the only modulators of myoma growth [2,3,4]. This can be explained with a presence of similar level of circulating hormone in women with and without myoma, with the occurrence of hormone-independent extrauterine leiomyoma and the possible absence of their regression in postmenopausal women [5].…”

Section: The Influence Of the Expression Of Steroid Receptors On Angimentioning

confidence: 99%

“…Recent studies showed local tissue-specific factors (for example, growth factors), as well as somatic mutations in pro and antiapoptotic genomes, participate in the pathogenesis and progression of these tumors, with or without cross-linking with mechanisms of action of steroid hormones. Among the environmental factors, particular attention is drawn to the presence and effect of estrogen and progesterone receptors on the endometrium and myometrial cells in the uterine wall with myoma [3].…”

Section: The Influence Of the Expression Of Steroid Receptors On Angimentioning

confidence: 99%

The influence of the expression of steroid receptors on angiogenesis, proliferation and apoptosis in myomas of pre- and postmenopausal women

et al. 2019

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Introduction/Objective The aim of this study was to determine the effects of the estrogen and progesterone receptor status on angiogenesis, proliferation, and apoptosis of myoma cells in premenopausal (PreM) and postmenopausal (PostM) women. Methods This was a cross section; clinical-experimental, retrospective, non-interventional study in the field of the study of fundamental pathogenesis mechanisms of disease using pathohistological materials from the existing archive. The research included 76 patients diagnosed with uterine leiomyomas, operatively treated in the Clinic for Gynecology and Obstetrics, Clinical Centre Kragujevac, Serbia. According to the menstrual status, we formed two experimental subgroups. The first group was PreM women (n = 35; 46.2 ± 5.02 years old), and the second group was PostM women (n = 41; 60.25 ± 5.41 years old). Hematoxylin-eosin staining for myoma and myometrium was conducted, as well as immunohistochemistry for ERα, ERβ, PRа, vascular endothelial growth factor, endoglin, Ki67, and caspase-3. Results Progesterone receptor was overexpressed in myoma and myometrium of PreM compared to myoma and myometrium of PostM women. Expression of caspase-3 was a statistically significant increase in PostM women compared to PreM group. ERα and ERβ were not changed among groups neither in myoma nor in myometrium samples. Conclusion According to our data, PRа had higher influence on apoptosis and cell growth than estrogen receptors. Since PRа was increased in PreM in both myoma and myometrium, probably this expression led further to lower expression of apoptotic marker in PreM women.

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Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

Cited by 18 publications

References 28 publications

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Ulipristal Acetate Inhibits Progesterone Receptor Isoform A-Mediated Human Breast Cancer Proliferation and BCl2-L1 Expression

The influence of the expression of steroid receptors on angiogenesis, proliferation and apoptosis in myomas of pre- and postmenopausal women

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