DNA Binding of the Glucocorticoid Receptor Is Not Essential for Survival

Reichardt, Holger M.; Kaestner, Klaus H.; Tuckermann, Jan; Kretz, Oliver; Wessely, Oliver; Böck, R.; Gass, Peter; Schmid, Wolfgang; Herrlich, Peter; Angel, Peter; Schütz, Günther

doi:10.1016/s0092-8674(00)81183-6

Cited by 987 publications

(854 citation statements)

References 47 publications

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“…It is known that Gc-induced apoptosis is dependant on sufficient levels of functional GR and subsequent alterations in gene expression. However, the mechanisms by which Gcs induce apoptosis differ between cell types (Reichardt et al, 1998;Schmidt et al, 2004). In lymphocytes, Gc treatment causes a downregulation of the anti-apoptotic genes, BCL-2 and BCL-xL (Herr et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells

et al. 2007

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“…NRs classically affect these processes as cisacting ligand-responsive switches to facilitate nucleation of factors to enhance or repress transcription. However, evidence suggests that in the absence of ligand, transcriptionally inactive NRs are not passive and may act in trans to sequester factors involved in other transcriptional pathways-expanding the physiologic role of NRs beyond either chromatin or ligand binding (Reichardt et al 1998;Lee et al 2003;Ogawa et al 2004). …”

Section: Nuclear Hormone Receptorsmentioning

confidence: 99%

Nuclear receptors, mitochondria and lipid metabolism

2008

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Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome proliferator activated receptors (PPARs) and Liver X receptors (LXRs), acting in concert with PPARγ Coactivator 1α (PGC-1α), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia, and obesity). Recently, additional partners of PGC-1α have moved to the forefront of metabolic research, the Estrogen-related Receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function.

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“…In addition, the transformation-promoting activity of the prototypic tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is inhibited by TIMPs 1 and 2 in culture (Shoji et al, 1997). Thus, the well-known ability of TPA to promote tumors in vivo may be partly due to its ability to upregulate MMP gene expression (Gack et al, 1994;Reichardt et al, 1998). On the other hand, TPA also upregulates TIMP-1 gene expression (Logan et al, 1996;Lu et al, 1991).…”

Section: Timps May Promote and Suppress Carcinogenesis By Distinct Mementioning

confidence: 99%

The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter

2000

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Extracellular matrix-degrading matrix metalloproteinases (MMPs) are invariably upregulated in epithelial cancers and are key agonists in angiogenesis, invasion and metastasis. Yet most MMPs are secreted not by the cancer cells themselves, but by stromal cells within and around the tumor mass. Because the stromal environment can in¯uence tumor formation, and because MMPs can alter this environment, MMPs may also contribute to the initial stages of cancer development. Several recent studies in MMP-overexpressing and MMP-de®cient mice support this possibility, but have required carcinogens or pre-existing oncogenic mutations to initiate tumorigenesis. Here we review the spontaneous development of premalignant and malignant lesions in the mammary glands of transgenic mice that express an autoactivating form of MMP-3/stromelysin-1 under the control of the whey acidic protein gene promoter. These changes were absent in nontransgenic littermates and were quenched by co-expression of a human tissue inhibitor of metalloproteinases-1 (TIMP-1) transgene. Thus by altering the cellular microenvironment, stromelysin-1 can act as a natural tumor promoter and enhance cancer susceptibility.

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DNA Binding of the Glucocorticoid Receptor Is Not Essential for Survival

Cited by 987 publications

References 47 publications

Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells

Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells

Nuclear receptors, mitochondria and lipid metabolism

The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter

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