Unique Roles of p160 Coactivators for Regulation of Breast Cancer Cell Proliferation and Estrogen Receptor-α Transcriptional Activity

Karmakar, Shilpi; Foster, Estrella; Smith, Carolyn L.

doi:10.1210/jcem.94.2.9992

Cited by 7 publications

(21 citation statements)

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“…Further, Bcl-2, an anti-apoptotic factor and chemoresistance marker, has previously been reported to be repressed by SRC-3 depletion in an ERα-and E2-dependent manner, whereas SRC-2 depletion had no effect on Bcl-2 expression in MCF-7 cells [10]. This is in contrast to our findings, where we detected Bcl-2 reduction by both stable SRC-2 knockdown [12] and transient CCNC depletion.…”

Section: Discussioncontrasting

confidence: 99%

“…Moreover, SRC-2 mediates hepatic glucose release during fasting and regulation of bile acid secretion [6,7], whereas absence of SRC-2 has been shown to protect against high-fat induced obesity [8]. It has also been shown that SRC-2 may have an oncogenic function in prostate cancer [9] as well as in breast cancer tissue, where its expression correlates with the expression of ERα [10]. During tumorigenesis, SRC-2 is initially increased in intraductal carcinomas compared to normal mammary glands.…”

Section: Introductionmentioning

confidence: 99%

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Cyclin C interacts with steroid receptor coactivator 2 and upregulates cell cycle genes in MCF-7 cells

Bozickovic

Hoang

Fenne

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Steroid receptor coactivator 2 (SRC-2) is a coactivator that regulates nuclear receptor activity. We previously reported that SRC-2 protein is degraded through the action of cAMP-dependent protein kinase A (PKA) and cAMP response element binding protein (CREB). In the study presented here, we aimed to identify proteins that interact with and thereby regulate SRC-2. We isolated cyclin C (CCNC) as an interacting partner with the SRC-2 degradation domain aa 347-758 in a yeast two-hybrid assay and confirmed direct interaction in an in vitro assay. The protein level of SRC-2 was increased with CCNC overexpression in COS-1 cells and decreased with CCNC silencing in COS-1 and MCF-7 cells. In a pulse-chase assay, we further show that silencing of CCNC resulted in a different SRC-2 degradation pattern during the first 6 h after the pulse. Finally, we provide evidence that CCNC regulates expression of cell cycle genes upregulated by SRC-2. In conclusion, our results suggest that CCNC temporarily protects SRC-2 against degradation and this event is involved in the transcriptional regulation of SRC-2 cell cycle target genes.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cyclin C interacts with steroid receptor coactivator 2 and upregulates cell cycle genes in MCF-7 cells

Bozickovic

Hoang

Fenne

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Here, we show that SRC-1 can play a critical role in surviving such glucose deprivation by altering the expression of complex I. This implicates SRC-1 in promoting a survival gene expression program upon depletion of glucose, consistent with the role of SRC-1 in promoting cell survival by promoting the expression of Bcl-2 (32).…”

Section: Discussionsupporting

confidence: 78%

Steroid Receptor Coactivator 1 is an Integrator of Glucose and NAD+/NADH Homeostasis

Motamed

Rajapakshe

Hartig

et al. 2014

Molecular Endocrinology

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Steroid receptor coactivator 1 (SRC-1) drives diverse gene expression programs necessary for the dynamic regulation of cancer metastasis, inflammation and gluconeogenesis, pointing to its overlapping roles as an oncoprotein and integrator of cell metabolic programs. Nutrient utilization has been intensely studied with regard to cellular adaptation in both cancer and noncancerous cells. Nonproliferating cells consume glucose through the citric acid cycle to generate NADH to fuel ATP generation via mitochondrial oxidative phosphorylation. In contrast, cancer cells undergo metabolic reprogramming to support rapid proliferation. To generate lipids, nucleotides, and proteins necessary for cell division, most tumors switch from oxidative phosphorylation to glycolysis, a phenomenon known as the Warburg Effect. Because SRC-1 is a key coactivator responsible for driving a hepatic gluconeogenic program under fasting conditions, we asked whether SRC-1 responds to alterations in nutrient availability to allow for adaptive metabolism. Here we show SRC-1 is stabilized by the 26S proteasome in the absence of glucose. RNA profiling was used to examine the effects of SRC-1 perturbation on gene expression in the absence or presence of glucose, revealing that SRC-1 affects the expression of complex I of the mitochondrial electron transport chain, a set of enzymes responsible for the conversion of NADH to NAD(+). NAD(+) and NADH were subsequently identified as metabolites that underlie SRC-1's response to glucose deprivation. Knockdown of SRC-1 in glycolytic cancer cells abrogated their ability to grow in the absence of glucose consistent with SRC-1's role in promoting cellular adaptation to reduced glucose availability.

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“…Knocking down SRC2 and SRC3 but not SRC1 inhibits growth of MCF7 cells and decreases cyclin D1 expression (39). Overexpression of SRC3 also increases breast cancer cell proliferation and invasiveness.…”

Section: Discussionmentioning

confidence: 99%

CARM1 Is an Important Determinant of ERα-Dependent Breast Cancer Cell Differentiation and Proliferation in Breast Cancer Cells

Al-Dhaheri

Skliris

et al. 2011

Cancer Research

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Breast cancers with estrogen receptor a (ERa) expression are often more differentiated histologically than ERa-negative tumors, but the reasons for this difference are poorly understood. One possible explanation is that transcriptional cofactors associated with ERa determine the expression of genes which promote a more differentiated phenotype. In this study, we identify one such cofactor as coactivator-associated arginine methyltransferase 1 (CARM1), a unique coactivator of ERa that can simultaneously block cell proliferation and induce differentiation through global regulation of ERa-regulated genes. CARM1 was evidenced as an ERa coactivator in cell-based assays, gene expression microarrays, and mouse xenograft models. In human breast tumors, CARM1 expression positively correlated with ERa levels in ER-positive tumors but was inversely correlated with tumor grade. Our findings suggest that coexpression of CARM1 and ERa may provide a better biomarker of well-differentiated breast cancer. Furthermore, our findings define an important functional role of this histone arginine methyltransferase in reprogramming ERa-regulated cellular processes, implicating CARM1 as a putative epigenetic target in ER-positive breast cancers. Cancer Res; 71(6); 2118-28. Ó2011 AACR.

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Unique Roles of p160 Coactivators for Regulation of Breast Cancer Cell Proliferation and Estrogen Receptor-α Transcriptional Activity

Cited by 7 publications

References 0 publications

Cyclin C interacts with steroid receptor coactivator 2 and upregulates cell cycle genes in MCF-7 cells

Cyclin C interacts with steroid receptor coactivator 2 and upregulates cell cycle genes in MCF-7 cells

Steroid Receptor Coactivator 1 is an Integrator of Glucose and NAD+/NADH Homeostasis

CARM1 Is an Important Determinant of ERα-Dependent Breast Cancer Cell Differentiation and Proliferation in Breast Cancer Cells

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