Epithelial c-jun and c-fos are temporally and spatially regulated by estradiol during neonatal rat oviduct differentiation

Okada, Akinobu; Ohta, Yasuhiko; Brody, Steven L.; Iguchi, Taisen

doi:10.1677/joe.0.1820219

Cited by 11 publications

(10 citation statements)

References 39 publications

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“…The explanation for this unexpected result might come from the fact that p38; (i) not a target of VHR, (ii) more importantly, activation of p38 after cellular stress might be a mechanism to arrest the growth of cells as well (through induction of Cdc25A degradation 37 ), which probably decreases Cyclin D1 expression as well. 34 Taken together, our studies identify BRCA1-IRIS as a component of the diverse signaling pathways that integrate multiple stimuli into an appropriate cellular response. Through MAPK and other downstream effectors, BRCA1-IRIS plays critical roles in many biological processes, especially in regulating cell growth.…”

Section: Discussionmentioning

confidence: 73%

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BRCA1‐IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR

Hao

ElShamy

2007

Intl Journal of Cancer

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Cyclin D1 plays an important role in cell cycle progression. In breast cancer, Cyclin D1 expression is deregulated by several mechanisms. We previously showed that in breast cancer cells, overexpression of BRCA1-IRIS induces Cyclin D1 overexpression and increases cell proliferation. BRCA1-IRIS alone or in complex with steroid receptor co-activators was targeted to the cyclin D1 promoter pre-bound by the c-Jun/AP1 and activated its transcription, which could explain the co-overexpression of BRCA1-IRIS and Cyclin D1 in breast cancer cells coupled with their increased proliferation. We report here an alternate or a complementary pathway by which BRCA1-IRIS activates Cyclin D1 expression. BRCA1-IRIS overexpression decreases the expression of the dual specificity phosphatase, DUSP3/VHR, an endogenous inhibitor of several MAPKs, including c-Jun N-terminal kinase. Although, the mechanism by which BRCA1-IRIS overexpression accomplishes that is not yet known, it is sufficient to induce Cyclin D1 overexpression in a human mammary epithelial cell model. Cyclin D1 overexpression could be blocked by co-overexpression of VHR in those cells. Furthermore, in 2 breast cancer cell lines that overexpress both BRCA1-IRIS and Cyclin D1 (MCF-7 and SKBR3) depletion of BRCA1-IRIS by RNA interference attenuated the expression of Cyclin D1 by elevating the expression level of VHR. These data demonstrate a critical role for BRCA1-IRIS in human breast cancer cell-cycle control and suggest that deregulated expression of BRCA1-IRIS is likely to reduce dependence on normal physiological growth stimuli, thereby providing a growth advantage to tumor cells and a potential mechanism of resistance to endocrine therapy. ' 2007 Wiley-Liss, Inc.Key words: BRCA1-IRIS; JNK; VHR; ErbB2; cyclin D1 Morphogenesis and development of mammary glands result from a complex interplay between genetic and epigenetic pathways that are controlled by hormones, growth factors, and other signaling molecules. Indeed, cyclin D1 2/2 mice show profound defects in mammary lobular-alveolar development, especially during pregnancy, because the breast epithelial cell compartment is unresponsive to ovarian steroids and fails to undergo the massive proliferative changes that these agents normally induce.

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Section: Discussionmentioning

confidence: 73%

“…32,34,35 Many patients with advanced breast cancer initially respond to hormonal therapy (e.g. tamoxifen) but in cases of recurrence, hormone-unresponsive tumors develop, 36 and they tend to be more aggressive, invasive and resistant to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

BRCA1‐IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR

Hao

ElShamy

2007

Intl Journal of Cancer

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“…Our prior studies in ciliated epithelial cells led us to investigate potentially shared features of airway and fallopian tube epithelium, especially given the common ciliated surface (22,23). Evidence supports critical roles for sex hormone regulation of cilia function in the fallopian tubes (15,(24)(25)(26).…”

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confidence: 98%

Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

Jain

Ray

Pan

et al. 2012

Am J Respir Cell Mol Biol

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Previous studies have demonstrated a female disadvantage in airway diseases, such as asthma and bronchiectasis. The basis for this sex disparity is unknown. We hypothesized that the female sex hormone, progesterone (P4), inhibits functions of the normal airway mucociliary apparatus. P4 receptor (PR) expression was evaluated in human lung and cultured primary human airway epithelial cells isolated from male and female lung transplant donors. PR expression was restricted to the proximal region of the cilia of airway epithelia, and was similar in men and women. Expression of isoform PR-B was more abundant than PR-A in cells from both sexes. Airway epithelial cell exposure to P4 decreased cilia beat frequency (CBF) by 42.3% (67.2). Inhibition of CBF was prevented by coadministration of P4 with the active form of estrogen, 17b-estradiol, or the PR antagonist, mifepristone. P4 inhibition was time and dose dependent, with a significant decrease by 8 hours and maximal effect at 24 hours, accompanied by translocation of PR from the cilia to the nucleus. Inhibition of cilia beat was also prevented by treatment of cells with actinomycin D, suggesting that CBF inhibition is a transcriptionally mediated event. Together, these findings indicate that sex hormones influence the function of a key component of the mucociliary apparatus. These mechanisms may contribute to the sex disparity present in airway diseases and provide therapeutic targets for the treatment of these debilitating airway diseases.Keywords: cilia; progesterone receptor; cilia beat frequency; sex disparity; lung diseaseMultiple epidemiologic studies have established that women have more severe airway disease than men (1, 2). Women with asthma and chronic obstructive lung disease have more frequent and severe exacerbations than men, and a lower disease-specific quality of life (1, 3). Bronchiectasis affects women more commonly, and is more aggressive than in men (2, 4). For example, in cystic fibrosis (CF), a disease in which the impact of bronchiectasis has been extensively studied, women have worse outcomes and a decreased life expectancy compared with men, despite a similar cause of disease. This has been attributed specifically to a greater severity of lung disease, and is present even after adjusting for potentially confounding morphometric, nutritional, compliance, and microbial factors (4, 5). In addition, in models of Pseudomonas aeruginosa infection, one of the most common pathogens found in bronchiectasis, female mice are more affected than males, again for unclear reasons (6). Defects in mucociliary clearance are a central component to the development of bronchiectasis. We, therefore, hypothesize that female sex hormones regulate the mucociliary apparatus.The major female sex hormones, estrogen and progesterone (P4), vary in levels during ovulatory cycles, pregnancy, menopause, and with exogenous delivery. Although their roles in the uterus, ovary, oviduct, and breast have been well studied, expression and function in other tissues are less well desc...

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“…It is recognized that all regions are composed of heterogeneous cell types: ciliated and secretory epithelial cells as well as smooth muscle cells (31). These cells can be distinguished by the expression of cell type-specific markers (39,47,50,68). In mammals it is likely that transport of the gametes, fertilization, initial embryonic development, and transport of the embryo to the uterus for implantation, a biological process, depend on the fallopian tube function (11,20).…”

mentioning

confidence: 99%

Ciliated epithelial-specific and regional-specific expression and regulation of the estrogen receptor-β2 in the fallopian tubes of immature rats: a possible mechanism for estrogen-mediated transport process in vivo

Shao¹,

Weijdegård²,

Fernández-Rodrı́guez³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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eral ER␤ isoforms have been identified in human and rodent tissues, but it is unclear whether each isoform has distinctly different cellular targeting characteristics and physiological functions. We have investigated the intracellular localization and regulatory patterns for ER␤ isoforms in rat fallopian tubes. Western blot analysis reveals that two ER␤ isoforms corresponding to ER␤1 and ER␤2 are expressed in rat fallopian tubes. However, ER␤2 is the predominant form of ER␤ in this tissue. High-resolution confocal imaging and immunohistochemical analysis provide ample evidence that ER␤ expression is limited almost exclusively to the ciliated epithelial cells, in contrast to ER␣, which is widely distributed. Furthermore, within the ciliated epithelial cells, ER␤ is colocalized with ␤-tubulin IV at stem portion of the cilia. We show that ER␤2 protein expression is tightly regulated by E 2 or DPN in a time-dependent manner without changes in ER␤1 expression. These estrogenic effects are inhibited by an ER antagonist, ICI 182,780. In addition, significant alteration of ER␤ immunoreactivity is detected only histologically in the ampullary region. Since the cilia are considered an essential determinant of tubal transport, we further demonstrate that E 2-or DPN-induced ER␤2 activation is associated with alterations in tubal protein expression crucial for the regulation of calcium-dependent ciliary beating. Given the coordinated regulation and interaction of ER and progesterone receptor in the cilia, we hypothesize that tubal ER␤2 may facilitate the estrogen-mediated transport process by processing protein-protein interaction under physiological and/or pathological conditions. We show for the first time that a previously unrecognized localization of ER␤ isoform in rat fallopian tubes can combine with estrogen to individually control the expression of ER ␤-isoforms in normal target tissues. estrogen receptor-␤ isoform; ciliated epithelial cells; ampulla

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Epithelial c-jun and c-fos are temporally and spatially regulated by estradiol during neonatal rat oviduct differentiation

Cited by 11 publications

References 39 publications

BRCA1‐IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR

BRCA1‐IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR

Sex Hormone–Dependent Regulation of Cilia Beat Frequency in Airway Epithelium

Ciliated epithelial-specific and regional-specific expression and regulation of the estrogen receptor-β2 in the fallopian tubes of immature rats: a possible mechanism for estrogen-mediated transport process in vivo

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