Histological and immunohistochemical evaluation of postmenopausal endometrium after 3 weeks of treatment with tibolone, estrogen only, or estrogen plus progestagen

Klaassens, Anet H.A.; Wijk, F. H. van; Hanifi-Moghaddam, Payman; Sijmons, Bianca; Ewing, Patricia C.; Kate-Booij, Marian J. Ten; Kooi, G.S.; Kloosterboer, Helenius J.; Blok, Leen J.; Burger, Curt W.

doi:10.1016/j.fertnstert.2005.12.077

Cited by 19 publications

(43 citation statements)

References 36 publications

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“…A description of the inclusion and exclusion criteria and of the histologic and molecular findings in the endometrium was documented earlier (1,24). The study groups were control group (8 subjects, no hormonal treatment), E 2 group (7 subjects, 2 mg of E 2 administered orally everyday, starting 21 d before surgery), and E 2 + MPA group (6 subjects, 2 mg E 2 + 5 mg MPA administered orally everyday, starting 21 d before surgery).…”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry and Western blotting were done essentially as described previously (1,29). The dilutions of antibody used in immunohistochemistry were rat monoclonal CD44 antibody, 1:1,000 (BD Pharmingen); rabbit monoclonal β-catenin antibody, 1:4,000 (Epitomics); and mouse progesterone receptor antibody, 1:50 (Ab-8 cocktail, Neomarkers).…”

Section: Immunohistochemistry and Western Blottingmentioning

confidence: 99%

“…In the first half of the regular menstrual cycle, the proliferation phase, E 2 is required to expand the endometrial layer by inducing cell proliferation. In the second half of the menstrual cycle, the secretory phase, progesterone levels increase, which antagonizes the proliferative activity of E 2 by inducing differentiation of epithelial and stromal cells of the endometrium (1). Thus, inhibition of E 2 -induced proliferation by progesterone is crucial for the maintenance of homeostasis in the endometrium.…”

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confidence: 99%

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Progesterone Inhibition of Wnt/β-Catenin Signaling in Normal Endometrium and Endometrial Cancer

Wang

Hanifi-Moghaddam

Hanekamp

et al. 2009

Clinical Cancer Research

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120

114

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Purpose. Wnt signaling regulates the fine balance between stemness and differentiation. Here, the role of Wnt signaling to maintain the balance between estrogen-induced proliferation and progesterone-induced differentiation during the menstrual cycle, as well as during the induction of hyperplasia and carcinogenesis of the endometrium, was investigated. Experimental Design: Endometrial gene expression profiles from estradiol (E 2 ) and E 2 + medroxyprogesterone acetate-treated postmenopausal patients were combined with profiles obtained during the menstrual cycle (PubMed; GEO DataSets). Ishikawa cells were transfected with progesterone receptors and Wnt inhibitors dickkopf homologue 1 (DKK1) and forkhead box O1 (FOXO1), measuring Wnt activation. Expression of DKK1 and FOXO1 was inhibited by use of sequence-specific short hairpins. Furthermore, patient samples (hormone-treated endometria, hyperplasia, and endometrial cancer) were stained for Wnt activation using nuclear β-catenin and CD44. Results: In vivo, targets and components of the Wnt signaling pathway (among them DKK1 and FOXO1) are regulated by E 2 and progesterone. In Wnt-activated Ishikawa cells, progesterone inhibits Wnt signaling by induction of DKK1 and FOXO1. Furthermore, using siRNA-mediated knockdown of both DKK1 and FOXO1, progesterone inhibition of Wnt signaling was partly circumvented. Subsequently, immunohistochemical analysis of the Wnt target gene CD44 showed that progesterone acted as an inhibitor of Wnt signaling in hyperplasia and in well-differentiated endometrial cancer. The female sex hormones estradiol (E 2 ) and progesterone play rate-limiting roles in the cyclical renewal of the inner layer of the uterus (endometrium). In the first half of the regular menstrual cycle, the proliferation phase, E 2 is required to expand the endometrial layer by inducing cell proliferation. In the second half of the menstrual cycle, the secretory phase, progesterone levels increase, which antagonizes the proliferative activity of E 2 by inducing differentiation of epithelial and stromal cells of the endometrium (1). Thus, inhibition of E 2 -induced proliferation by progesterone is crucial for the maintenance of homeostasis in the endometrium.Increased estrogen signaling often underlies endometrial hyperplasia and is a well-established risk factor for endometrial cancer (2). Because progesterone inhibits estrogen-induced endometrial proliferation, progesterone has been used in its synthetic form [i.e., medroxyprogesterone acetate (MPA)] in palliative treatment of advanced and recurrent endometrial cancer with modest though significant response rates (15-25%; ref. 3). Progesterone has also been used as a primary treatment for endometrial carcinoma confined to the endometrial layer of the uterus, for example, in premenopausal women determined to preserve fertility. Response rates in these women can be up to 60% (4, 5), indicating that progesterone signaling in well-differentiated endometrial cancer is a potent inhibitor of endometrial carcinogene...

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Section: Methodsmentioning

confidence: 99%

Section: Immunohistochemistry and Western Blottingmentioning

confidence: 99%

mentioning

confidence: 99%

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Progesterone Inhibition of Wnt/β-Catenin Signaling in Normal Endometrium and Endometrial Cancer

Wang

Hanifi-Moghaddam

Hanekamp

et al. 2009

Clinical Cancer Research

Self Cite

120

114

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“…In order to do this we have used patient data from two earlier investigations from our group (For complete details see [25,26]. In short the following patient-groups have been included:…”

Section: Patients and Tissuesmentioning

confidence: 99%

Signaling by estrogens and tamoxifen in the human endometrium

Gielen

Santegoets

Hanifi-Moghaddam

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

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“…Immunohistochemistry was performed essentially as described before (Klaassens et al, 2006). The antibodies employed are: mouse monoclonal anti-SMA (DAKO, Heverlee, Belgium) (1:150), rat monoclonal anti-cytokeratine 8 (CK8, 1:5000) (DSHB, Iowa, USA), rabbit polyclonal anti-ERα (Millipore, Billerica, USA) (1:2000) and rabbit monoclonal anti-β-catenin (Epitomics, Burlingame, USA) (1:800).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Loss of APC function in mesenchymal cells surrounding the Müllerian duct leads to myometrial defects in adult mice

Wang¹,

Jia²,

Franken³

et al. 2011

Molecular and Cellular Endocrinology

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Histological and immunohistochemical evaluation of postmenopausal endometrium after 3 weeks of treatment with tibolone, estrogen only, or estrogen plus progestagen

Cited by 19 publications

References 36 publications

Progesterone Inhibition of Wnt/β-Catenin Signaling in Normal Endometrium and Endometrial Cancer

Progesterone Inhibition of Wnt/β-Catenin Signaling in Normal Endometrium and Endometrial Cancer

Signaling by estrogens and tamoxifen in the human endometrium

Loss of APC function in mesenchymal cells surrounding the Müllerian duct leads to myometrial defects in adult mice

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