Interleukin 1 regulates human metallothionein gene expression.

Karin, Michael; Imbra, Richard J.; Heguy, Adriana; Wong, Grace

doi:10.1128/mcb.5.10.2866

Cited by 163 publications

(53 citation statements)

References 33 publications

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“…As a variety of endogenous factors (e.g. glucocorticosteroids, ILs, IFNg, TNF-a) are involved in the induction of the synthesis of intracellular MT, one may suggest that this may lead to an overprotection of tumour cells against apoptosis, and, on the other hand, supporting the metastatic behaviour of the tumour (Karin et al, 1985;Karasawa et al, 1987;Nath et al, 1988;Schroeder and Cousins, 1990;Sato and Sasaki, 1992;Tsangaris and TzortzatouStathopoulou, 1998;Miles et al, 2000;Nishimura et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…They can protect cells against UV-/ionic radiation (Hansen et al, 1997;Hanada et al, 1998;Reeve et al, 2000) as well as cytotoxic alkylating agents including chemotherapeutics (Chin et al, 1993;Hishikawa et al, 1997;Okazaki et al, 1998;Sunada et al, 2005), modulate oxygen free radicals and nitric oxide and inhibit apoptosis (Tsangaris and Tzortzatou-Stathopoulou, 1998). The synthesis of MT is induced by group II heavy metal ions as well as by endogenous factors such as glucocorticoids, cytokines (interleukin (IL)-1 or IL-6, interferon g (IFNg), tumour necrosis factor a (TNF-a)) or vitamin D 3 (Karin et al, 1985;Karasawa et al, 1987;Schroeder and Cousins, 1990;Sato and Sasaki, 1992;Nishimura et al, 2000). There is also some evidence that inflammatory stressors (e.g.…”

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confidence: 99%

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Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

et al. 2006

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Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel -Haenszel w 2 test, Kaplan -Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (Po0.0001). Similarly, Kaplan -Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2 -10.2; Po0.0001 for progression; relative risk 7.1; 95% CI 4.7 -10.9; Po0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

et al. 2006

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“…MT gene expression is predominantly regulated at the level of transcription [5][6][7][8][9]. Though the mechanism of regulation is poorly understood, rapid induction occurs upon exposure to metals [5] and, in mammalian cells, to various circulating factors such as glucocorticoid hormones [6], ainterferon [7], and interleukin-1 and other mediators of the inflammatory response [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Though the mechanism of regulation is poorly understood, rapid induction occurs upon exposure to metals [5] and, in mammalian cells, to various circulating factors such as glucocorticoid hormones [6], ainterferon [7], and interleukin-1 and other mediators of the inflammatory response [8,9]. It has been suggested that a common pathway for MT induction involves protein kinase C (PKC) activation since MT levels increase in serum-starved cells after treatment with growth factors and TPA, agents which function in part through PKC activation [10,11].…”

Section: Introductionmentioning

confidence: 99%

Metallothionein RNA levels in HL‐60 cells Effect of cadmium, differentiation, and protein kinase C activation

1988

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Metallothionein (MT) gene transcription is regulated in a developmental and tissue-specific manner by metal ions and other agents. We examined MT expression in the human promyelocytic leukemia cell line HL-60 during differentiation along macrophage and neutrophil lineages. All HL-60 phenotypes showed similar basal levels of MT RNA with significant induction following exposure to Cd 2+ but not activators of PKC. MT RNA did not correlate with growth state or with known levels of PKC activity, thus our data do not support a role for MT in HL-60 differentiation or for PKC in MT expression.

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“…(rC) and this probably reflects the fact that IL-1 is a weaker gene activator than interferon on epithelial and fibroblastic cells. This is the case for the metallothionein I1 gene which is also inducible by interferon but which is only weakly induced by IL-1 in some cell lines and not in others [16].…”

Section: Three Irs-like Sequences Are Present In the Ifi-56k Promotermentioning

confidence: 99%

New inducers revealed by the promoter sequence analysis of two interferon-activated human genes

et al. 1987

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In order to investigate the molecular basis of the regulation of interferon-inducible genes, we isolated the promoter region of two such genes coding for the (2'-S')oligo(adenylate) synthetase and a 56-kDa protein (IFI-56K). The regions surrounding the cap site were sequenced and compared with the sequences of vertebrate and viral DNA present in the Genbank data bank. Small DNA segments were found in both genes which are homologous to part of the promoter region of other genes, such as those of interferon-p, tumor necrosis factor / 3, interleukin-2 and its receptor. Since these homologies were found located in functionally important regions of these genes, we tested whether their inducers also enhance the (2'-5')oligo(adenylate) synthetase and IFI-56K gene expression. We found that poly(r1) . poly(rC) and interleukin-1, activators of the interferon-p gene and of T lymphocytes respectively, are both able to enhance IFI-56K mRNA accumulation in all cell lines tested.Cycloheximide even superinduces this gene when added together with poly(r1) . poly(rC) and interleukin-1 (but not when added with interferon). We showed that these inductions are direct and not mediated by interferon produced by cells in response to poly(r1) . poly(rC) or interleukin-1 . The promoter sequence analyses have thus led to the discovery of unexpected inducers, i.e. an interferon inducer such as poly(r1) . poly(rC) is also able to directly induce a gene that is under the control of interferon.Interferons are proteins or glycoproteins secreted by various cells in response to viral infection or other stimuli. They are defined by their antiviral activity, i.e. protection against subsequent infection by different viruses of pretreated, metabolically active cells. Beside the establishment of an antiviral state, interaction between interferon and its receptor on the cell surface also leads to a wide range of biological effects, such as the inhibition of cell growth and modulations of the immune system (for reviews see [l, 21. In that way interferons, as other cytokines, act as pleiotropic effectors, since they modify not only the biochemistry of some target cells but also the physiology of the entire organism. Conversely it has been suggested that some other cytokines (tumor necrosis factors c( and p [3,41) have intrinsic antiviral activities.Numerous cDNAs corresponding to interferon-inducible genes have been cloned but the biological function of these genes has been discovered in a few cases only. Their transcriptional regulation appears to be rather complex. Indeed, all the genes studied so far seem to behave differently with respect to their kinetics of mRNA accumulation after interferon treatment. Moreover, for a given gene, the response to interferon treatment is dependent on the type of interferon and target cell used [5 -111. Finally, amongst these genes, only some remain inducible in interferon-resistant lymphoblastoid (Daudi) cells, demonstrating the existence of at least two different pathways of induction downstream from the interacti...

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Interleukin 1 regulates human metallothionein gene expression.

Cited by 163 publications

References 33 publications

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

Metallothionein RNA levels in HL‐60 cells Effect of cadmium, differentiation, and protein kinase C activation

New inducers revealed by the promoter sequence analysis of two interferon-activated human genes

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