Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

Bircan, Sema; Ensarı, Arzu; Öztürk, Sibel; Erdoğan, Nural; Dundar, Ilkkan; Ortaç, Fırat

doi:10.1007/bf03032403

Cited by 37 publications

(40 citation statements)

References 43 publications

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“…Bircan et al . showed, using immunohistochemistry, that c-jun expression occurs primarily in the proliferative phase of the menstrual cycle 80 , which was further supported by Hong et al . showing a correlation between growth in cultured endometrial stromal cells and activated c-jun expression 81 .…”

Section: Expression and Localization Of E2-erα C-fos C-jun And C-msupporting

confidence: 55%

Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

2009

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The p38 mitogen-activated protein kinases (MAPKs) are members of discrete signal transduction pathways that have significant regulatory roles in a variety of biological processes, depending on the cell, tissue and organ type. p38 MAPKs are involved in inflammation, cell growth and differentiation and cell cycle. In the female reproductive system, p38 MAPKs are known to regulate various aspects of the reproductive process such as mammalian estrous and menstrual cycles as well as early pregnancy and parturition. p38 MAPKs have also been implicated in alterations and pathologies observed in the female reproductive system. Therefore, pharmacologic modulation of p38 MAPKs, and inter-connected signaling pathways (e.g., estrogen receptor signaling, c-fos, c-jun), may influence reproductive physiology and function. This article provides a critical, comparative review of available data on the roles of p38 MAPKs in the mammalian female reproductive system and in reproductive pathophysiology in humans and preclinical species. We first introduce fundamental differences and similarities of the mammalian female reproductive system that should be considered by toxicologists and toxicologic pathologists when assessing the effects of new pharmacologic agents on the female reproductive system. We then explore in detail the known roles for p38 MAPKs and related molecules in female reproduction. This foundation is then extended to pathological conditions in which p38 MAPKs are thought to play an integral role.

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Section: Expression and Localization Of E2-erα C-fos C-jun And C-msupporting

confidence: 55%

Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

2009

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“…The decrease in ERa expression confers dual implication with regard to tamoxifentreated uterus: First, the ER-related signaling, known to mediate hyperplastic response, is diminished, and, second, the uterine response to tamoxifen is reduced because there are less tamoxifenbinding receptors per cell. c-Myc protein, known to induce proliferation and to play a role in the development of endometrial carcinoma (41), is upregulated by tamoxifen (42,43). In our mice model tamoxifen treatment causes an increase in the level of c-Myc protein, compared with its level in control mice.…”

Section: Discussionmentioning

confidence: 78%

Pigment Epithelium–Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia

Goldberg

Bar‐Joseph

Grossman

et al. 2015

Molecular Cancer Therapeutics

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Tamoxifen is a cornerstone component of adjuvant endocrine therapy for patients with hormone-receptor-positive breast cancer. Its significant adverse effects include uterine hyperplasia, polyps, and increased risk of endometrial cancer. However, the underlying molecular mechanism remains unclear. Excessive angiogenesis, a hallmark of tumorigenesis, is a result of disrupted balance between pro-and anti-angiogenic factors. VEGF is a proangiogenic factor shown to be elevated by tamoxifen in the uterus. Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic factor that suppresses strong pro-angiogenic factors, such as VEGF. Our aim was to investigate whether angiogenic balance plays a role in tamoxifen-induced uterine pathologies, elucidate the molecular impairment in that network, and explore potential intervention to offset the proposed imbalance elicited by tamoxifen. Using in vivo mouse models, we demonstrated that tamoxifen induced a dose-dependent shift in endogenous uterine angiogenic balance favoring VEGF over PEDF. Treatment with recombinant PEDF (rPEDF) abrogated tamoxifen-induced uterine hyperplasia and VEGF elevation, resulting in reduction of blood vessels density. Exploring the molecular mechanism revealed that tamoxifen promoted survival and malignant transformation pathways, whereas rPEDF treatment prevents these changes. Activation of survival pathways was decreased, demonstrated by reduction in AKT phosphorylation concomitant with elevation in JNK phosphorylation. Estrogen receptor-a and c-Myc oncoprotein levels were reduced. Our findings provide novel insight into the molecular mechanisms tamoxifen induces in the uterus, which may become the precursor events of subsequent endometrial hyperplasia and cancer. We demonstrate that rPEDF may serve as a useful intervention to alleviate the risk of tamoxifen-induced endometrial pathologies.

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“…The overexpression or amplification of c-Myc was observed in many types of cancers [43]. It was also proven that c-Myc could play important roles in cancer cell growth, apoptosis, metabolism, and cell differentiation [44]. Since it was demonstrated that E2 treatment could enhance the c-Myc expression in ovarian cancer cells [45], inhibition of c-Myc expression through blocking estrogen signaling may also contribute to the suppression of cancer progression.…”

Section: Discussionmentioning

confidence: 99%

The Wedelolactone Derivative Inhibits Estrogen Receptor-Mediated Breast, Endometrial, and Ovarian Cancer Cells Growth

Lin

Yeh

et al. 2014

BioMed Research International

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Estrogen and estrogen receptor (ER)-mediated signaling pathways play important roles in the etiology and progression of human breast, endometrial, and ovarian cancers. Attenuating ER activities by natural products and their derivatives is a relatively practical strategy to control and reduce breast, endometrial, and ovarian cancer risk. Here, we found 3-butoxy-1,8,9-trihydroxy-6H-benzofuro[3,2-c]benzopyran-6-one (BTB), a new derivative of wedelolactone, could effectively inhibit the 17-estradiol (E2)-induced ER transactivation and suppress the growth of breast cancer as well as endometrial and ovarian cancer cells. Our results indicate that 2.5 μM BTB effectively suppresses ER-positive, but not ER-negative, breast, endometrial, and ovarian cancer cells. Furthermore, our data indicate that BTB can modulate ER transactivation and suppress the expression of E2-mediated ER target genes (Cyclin D1, E2F1, and TERT) in the ER-positive MCF-7, Ishikawa, and SKOV-3 cells. Importantly, this BTB mediated inhibition of ER activity is selective since BTB does not suppress the activities of other nuclear receptors, including glucocorticoid receptor and progesterone receptor, suggesting that BTB functions as a selective ER signaling inhibitor with the potential to treat breast, endometrial, and ovarian cancers.

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Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

Cited by 37 publications

References 43 publications

Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

Pigment Epithelium–Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia

The Wedelolactone Derivative Inhibits Estrogen Receptor-Mediated Breast, Endometrial, and Ovarian Cancer Cells Growth

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