Expression of c-Myc in glucocorticoid-treated fibroblastic cells

Frost, Gloria H.; Rhee, Kunsoo; Ma, Tianlin; Thompson, E. Aubrey

doi:10.1016/0960-0760(94)90017-5

Cited by 16 publications

(7 citation statements)

References 39 publications

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“…Glucocorticoids influence many fundamental biological processes, from development and homeostasis to proliferation, differentiation and apoptosis [2,3]. In many cell types, they promote arrest in the G1-S transition of the cell cycle, resulting in a decrease in proliferation [4][5][6]. Glucocorticoids are used as part of anticancer therapy for some lymphatic leukemias and lymphomas [7].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of glucocorticoid receptor expression by RNA interference promotes cell proliferation in murine macrophage RAW264.7 cells

Zhu

Liu

Lü

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Introductionmentioning

confidence: 99%

Knockdown of glucocorticoid receptor expression by RNA interference promotes cell proliferation in murine macrophage RAW264.7 cells

Zhu

Liu

Lü

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…This anti-proliferative effect is normally represented by arresting the cells in the G 1 -phase of the cell cycle (Sanchez et al 1993, Frost et al 1994, Rhee et al 1995, Corroyer et al 1997, Rogatsky et al 1997. Progression through G 1 -and entry into S-phase is positively regulated by the activation of cyclindependent kinase 2 (CDK2), which is complexed with cyclin A or cyclin E (Sherr 1993).…”

Section: Introductionmentioning

confidence: 99%

Identification of a functional glucocorticoid response element in the promoter of the cyclin-dependent kinase inhibitor p57Kip2

Alheim

Corness²,

Samuelsson³

et al. 2003

Journal of Molecular Endocrinology

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Glucocorticoids are known regulators of the cell cycle, normally exerting an anti-proliferative effect. We have previously shown that glucocorticoids stimulate expression of p57 Kip2 , a member of the Cip/Kip family of cyclin-dependent kinase inhibitors which, in some cell types, may account for the anti-proliferative responses seen after glucocorticoid treatment. The induction of p57Kip2 involves primary transcriptional effects where no de novo protein synthesis is necessary, suggesting a direct interaction of the glucocorticoid receptor with the p57 Kip2 gene. In this study we have identified a functional glucocorticoid response element (GRE), located 5 kilo bases (kb) upstream of the transcription start site in the human p57Kip2 promoter. This GRE was functional also when isolated, suggesting a direct transcriptional effect of the glucocorticoid receptor. Furthermore, mutation of this GRE abolished glucocorticoid induction of the reporter gene, whereas mutation of a nearby Sp1 site did not. Using electrophoretic mobility shift assays, we have shown that the -5 kb p57Kip2 promoter GRE was able to compete with a well-known GRE for glucocorticoid receptor binding. Sequence comparisons with the mouse genome showed that this GRE is highly conserved, further strengthening the biological importance of this site. All these data emphasize the involvement of this GRE in the glucocorticoid-mediated induction of p57 Kip2 expression.

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“…Glucocorticoids can induce a G 1 cell cycle arrest and programmed cell death of immature thymocytes, several leukemic cell lines, and mature peripheral T lymphocytes (1,63,74). They also inhibit the proliferation of mammary epithelial cells (4,22,69), fibroblasts (18), and hepatoma cells (11,52) and induce differentiation of osteoblasts (46,54). Although these diverse effects of glucocorticoid hormones have been well documented, the mechanism by which these effects are induced remains unclear.…”

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confidence: 99%

Glucocorticoid Receptor-Mediated Cell Cycle Arrest Is Achieved through Distinct Cell-Specific Transcriptional Regulatory Mechanisms

Rogatsky

Trowbridge

Garabedian

1997

Molecular and Cellular Biology

241

209

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Glucocorticoids inhibit proliferation of many cell types, but the events leading from the activated glucocorticoid receptor (GR) to growth arrest are not understood. Ectopic expression and activation of GR in human osteosarcoma cell lines U2OS and SAOS2, which lack endogenous receptors, result in a G 1 cell cycle arrest. GR activation in U2OS cells represses expression of the cyclin-dependent kinases (CDKs) CDK4 and CDK6 as well as their regulatory partner, cyclin D3, leading to hypophosphorylation of the retinoblastoma protein (Rb). We also demonstrate a ligand-dependent reduction in the expression of E2F-1 and c-Myc, transcription factors involved in the G 1 -to-S-phase transition. Mitogen-activated protein kinase, CDK2, cyclin E, and the CDK inhibitors (CDIs) p27 and p21 are unaffected by receptor activation in U2OS cells. The receptor's N-terminal transcriptional activation domain is not required for growth arrest in U2OS cells. In Rb-deficient SAOS2 cells, however, the expression of p27 and p21 is induced upon receptor activation. Remarkably, in SAOS2 cells that express a GR deletion derivative lacking the N-terminal transcriptional activation domain, induction of CDI expression is abolished and the cells fail to undergo ligand-dependent cell cycle arrest. Similarly, murine S49 lymphoma cells, which, like SAOS2 cells, lack Rb, require the N-terminal activation domain for growth arrest and induce CDI expression upon GR activation. These cell-type-specific differences in receptor domains and cellular targets linking GR activation to cell cycle machinery suggest two distinct regulatory mechanisms of GR-mediated cell cycle arrest: one involving transcriptional repression of G 1 cyclins and CDKs and the other involving enhanced transcription of CDIs by the activated receptor.

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Expression of c-Myc in glucocorticoid-treated fibroblastic cells

Cited by 16 publications

References 39 publications

Knockdown of glucocorticoid receptor expression by RNA interference promotes cell proliferation in murine macrophage RAW264.7 cells

Knockdown of glucocorticoid receptor expression by RNA interference promotes cell proliferation in murine macrophage RAW264.7 cells

Identification of a functional glucocorticoid response element in the promoter of the cyclin-dependent kinase inhibitor p57Kip2

Glucocorticoid Receptor-Mediated Cell Cycle Arrest Is Achieved through Distinct Cell-Specific Transcriptional Regulatory Mechanisms

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