Calmodulin, a regulatory partner of the estrogen receptor alpha in breast cancer cells

Gallo, Dominique; Jacquot, Yves; Laurent, Guy; Leclercq, Guy

doi:10.1016/j.mce.2008.04.011

Cited by 39 publications

(35 citation statements)

References 73 publications

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“…Numerous differentially regulated genes have been implicated in ER-mediated actions (functional theme E in Tables 2 and 3), which are typified by calmodulin (18,30), hsp90b (10,29), O-GlcNAc transferase (7), UCE2 variant 1 (39,59), and the dynein light chain (22,48). The expression change of calmodulin was verified by real-time PCR in the current study.…”

Section: Discussionsupporting

confidence: 61%

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish

Zhang

Popesku

Martyniuk

et al. 2009

Physiological Genomics

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Teleost fish represent unique models to study the role of neuroestrogens because of the extremely high activity of brain aromatase (AroB; the product of cyp19a1b). Aromatase respectively converts androstenedione and testosterone to estrone and 17␤-estradiol (E2). Specific inhibition of aromatase activity by fadrozole has been shown to impair estrogen production and influence neuroendocrine and reproductive functions in fish, amphibians, and rodents. However, very few studies have identified the global transcriptomic response to fadrozole-induced decline of estrogens in a physiological context. In our study, sexually mature prespawning female goldfish were exposed to fadrozole (50 g/l) in March and April when goldfish have the highest AroB activity and maximal gonadal size. Fadrozole treatment significantly decreased serum E2 levels (4.7 times lower; P ϭ 0.027) and depressed AroB mRNA expression threefold in both the telencephalon (P ϭ 0.021) and the hypothalamus (P ϭ 0.006). Microarray expression profiling of the telencephalon identified 98 differentially expressed genes after fadrozole treatment (q value Ͻ0.05). Some of these genes have shown previously to be estrogen responsive in either fish or other species, including rat, mouse, and human. Gene ontology analysis together with functional annotations revealed several regulatory themes for physiological estrogen action in fish brain that include the regulation of calcium signaling pathway and autoregulation of estrogen receptor action. Real-time PCR verified microarray data for decreased (activin-␤A) or increased (calmodulin, ornithine decarboxylase 1) mRNA expression. These data have implications for our understanding of estrogen actions in the adult vertebrate brain.aromatase; microarray; fish; brain MAIN ESTROGENS estradiol-17␤ (E2) and estrone (E1) play fundamental regulatory roles in neuroendocrine and reproductive systems. Through binding to its nuclear estrogen receptors (nER)-␣ and nER-␤, E2 regulates transcriptional process of target genes whose promoters contain estrogen-responsive elements (ERE) (57). In addition to this classical nuclear action, E2 also has membrane actions in which a unique membrane receptor is utilized to rapidly activate a series of signaling pathways (52,70). Since the signaling pathway activation will ultimately influence the transcriptional activities of downstream transcription factors including nERs, membrane actions of E2 provide another mode to regulate genomic gene expression (70). Fish are unique models in which to study E2 action because there is high activity of the B-subtype aromatase (AroB; the product of cyp19a1b), the enzyme responsible for synthesizing E2 from testosterone (T), in the neuroendocrine brain, telencephalon (Tel) and hypothalamus (Hyp) (42). Moreover, in contrast to mammals where aromatase and nER are commonly expressed in neurons, current studies in fish and birds strongly suggest that AroB is exclusively expressed in radial glial cells and nER is mostly expressed in neurons (16,43). Thus, the local...

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Section: Discussionsupporting

confidence: 61%

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish

Zhang

Popesku

Martyniuk

et al. 2009

Physiological Genomics

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“…As such, these proteins might have the potential to be putative breast cancer markers. As expected, some well-known breast cancer markers, such as 14-3-3 proteins (Danes et al, 2008), annexins (Cao et al, 2008a), calmodulin (Gallo et al, 2008), anterior gradient homolog 2 (AGR-2) (Zweitzig et al, 2007;Fritzsche et al, 2006), Galectin-1 (Jung et al, 2007) and Rho-associated protein kinase-2 (ROCK2) (Fu et al, 2008b), were also identified in this 2D-DIGE experiment, lending credence to the reliability of early phase biomarker detection using this experimental strategy. Fig.…”

Section: D-dige and Maldi-tof Ms Analysis Of Total Intracellular Prosupporting

confidence: 79%

Proteomic Analysis of Potential Breast Cancer Biomarkers

Chou¹,

Chan²

2011

Breast Cancer - Recent Advances in Biology, Imaging and Therapeutics

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“…Cytosolic and nuclear Ca 2ϩ levels serve as a second messenger in the cell (41, 42) that controls biosynthesis and/or signaling of E2 (43). Our model illustrates how ER-␣ might integrate estrogen signals and calcium cascades during signal transduction to control gene expression in neurons (44) and breast cancer cells (11). The mechanism in Fig.…”

Section: Discussionmentioning

confidence: 90%

Structural Basis for Ca2+-induced Activation and Dimerization of Estrogen Receptor α by Calmodulin

Zhang

Sacks

et al. 2012

Journal of Biological Chemistry

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Calmodulin, a regulatory partner of the estrogen receptor alpha in breast cancer cells

Abstract: International audienc

Cited by 39 publications

References 73 publications

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish

Profiling neuroendocrine gene expression changes following fadrozole-induced estrogen decline in the female goldfish

Proteomic Analysis of Potential Breast Cancer Biomarkers

Structural Basis for Ca2+-induced Activation and Dimerization of Estrogen Receptor α by Calmodulin

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