Inhibitory effect of estrogen on Rac1-expression in monocytes

Adam, Oliver; Hagel, Marion; Theobald, Katharina; Böhm, Michael; Laufs, Ulrich

doi:10.1016/j.bbrc.2009.05.126

Cited by 7 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rac1 activity can regulate estrogen receptor transcriptional activity positively in human breast cancer cell lines (33). In contrast to BPA, estrogen has been reported to regulate Rac1 expression negatively in monocytes (34) and vascular smooth muscle cells (35), although in the present study E2 treatment did not alter Rac1 expression significantly. We speculate that through its positive regulation of Rac1 levels BPA may function as an estrogen sensitizer by antagonizing a negative feedback loop of estrogen on Rac1 levels.…”

Section: Functional Classes Of Proteins and Pathways Changed By Exposcontrasting

confidence: 79%

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Williams

Lemieux

Hassis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl 153 (PCB153) on the proteome of primary organotypic cultures of the mouse mammary gland. At low-nanomolar doses each of these agents induced distinct effects on the proteomes of these cultures. Although BPA treatment produced effects that were similar to those induced by estradiol, there were some notable differences, including a reduction in the abundance of retinoblastomaassociated protein and increases in the Rho GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle protein CDC42. Both Pht and PCB153 induced changes that were distinct from those induced by estrogen, including decreased levels of the transcriptional corepressor C-terminal binding protein 1. Interestingly, the three chemicals appeared to alter the abundance of distinct splice forms of many proteins as well as the abundance of several proteins that regulate RNA splicing. Our combined results indicate that the three classes of chemical have distinct effects on the proteome of normal mouse mammary cultures, some estrogen-like but most estrogen independent, that influence diverse biological processes including apoptosis, cell adhesion, and proliferation.proteomics | mammary epithelium | environmental chemicals | organotypic culture | estrogen B reast cancers are caricatures of normal tissue development (1-3). The same underlying mechanisms that affect the cell processes needed for normal mammary development contribute to cancer progression. By affecting the distribution of interacting cells and communication among them through nontargeted effects, carcinogens can promote the outgrowth of altered cells with malignant potential. Exposure to environmental agents can affect mammary gland development and alter breast cancer risk. Epidemiologic studies have associated a number of environmental factors with increased breast cancer risk (4). Some of these factors may have low-level effects that are not genotoxic but alter immune responses, vascularity, or the microenvironment or that change susceptibility to carcinogens. A current weakness in models of cancer risk assessment is the lack of consideration of factors that influence the susceptibility of mixed cell populations to transformation. Indeed, ionizing radiation, the prototypical carcinogen, promotes changes in the biochemical properties in cultured mouse and human breast cells, in the stromal environment, and in intact mouse mammary gland (5-7).Physiologically relevant 3D culture models can recapitulate crucial aspects of the dynamic and reciprocal signaling necessary for establishing and maintaining tissue-specific morphogenetic programs. The determination of the molecular mechanisms underlying m...

show abstract

Section: Functional Classes Of Proteins and Pathways Changed By Exposcontrasting

confidence: 79%

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Williams

Lemieux

Hassis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Ovariectomized spontaneously hypertensive mice also show increased vascular Rac mRNA that is reversed with E treatment [41]. Ovariectomy induces similar effects in monocytes [42]. A direct impact of altered Rac expression in mammary fat pad on epithelial cell proliferation, which is located several millimeters away, is difficult to explain.…”

Section: Discussionmentioning

confidence: 99%

Effect of exogenous somatotropin and staged ovariectomy on mRNA expression of select ECM-related proteins in mammary tissue of prepubertal Holstein calves

Huderson¹,

Velayudhan²,

Pearson³

et al. 2013

OJAS

View full text Add to dashboard Cite

Growth hormone (GH) and estrogen are essential stimulators of mammary cell proliferation and mammary development as mammals near puberty. Mammary ductal growth requires modifications of the extracellular matrix (ECM) for this tissue expansion to occur. Our purpose was to evaluate the effects of exogenous GH and ovariectomy (known to impact estrogen production) on gene expression of selected ECM proteins in the mammary parenchyma (PAR) and mammary fat pad (MFP) of prepubertal calves. Our hypothesis was that both GH and ovariectomy would alter the mRNA expression of multiple mammary ECM proteins. However, treatment with GH significantly reduced the expression of only fibronectin in PAR. However, the mRNA expression of all of the ECM proteins tested was numerically lower in PAR from GH treated calves. In contrast, staged ovariectomy decreased expression of fibronectin and heat shock protein 90 but increased expression of epimorphin in mammary PAR. In the MFP expression of Rac-1 and fascin were increased. These findings suggest that effects of exogenous GH on mammary gland composition are only marginally dependent on alterations in ECM proteins but the more pronounced effects of ovariectomy (reduced PAR mass and altered myoepithelial ontogeny) are more likely linked to changes in expression of ECM proteins.

show abstract

“…14 A decrease of Rac1 expression by estrogen was completely blocked in the presence of a nonselective estrogen receptor (ER) antagonist, suggesting a receptor-mediated event. 15 Ex vivo studies have shown that ER can bind to the regulatory subunit, p85a, of phosphatidylinositol-3-OH kinase leading to enhanced activation of Akt in the presence of estrogen. 16 Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes and activated Akt can phosphorylate Rac1 at Ser71 reducing Rac1 activation.…”

mentioning

confidence: 99%