Disease relevance of MT1G

• Our studies show that the MT-IF and MT-IG genes are differentially regulated in two human hepatoma cell lines, HepG2 and Hep3B2, and a human lymphoblastoid cell line, WI-L2 in response to the heavy metals cadmium, zinc and copper, and glucocorticoids [1].
• MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule [2].
• Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment.RESULTS: MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples [2].
• The expression of three human metallothionein genes, MT-IIA, MT-IF, and MT-IG was studied in the human hepatoblastoma (HepG2), the hepatocarcinoma (Hep3B2), the embryonic kidney (Hek 293), and the lymphoblastoid-derived (Wi-L2) cell lines [3].
• Expression of a dominant-positive G(alphai2) protein, with which the MT1 receptor has been shown to couple, is able to mimic the effect of melatonin on ERalpha but not RARalpha transcriptional activation in breast cancer cells [4].

High impact information on MT1G

• This phenotype was mimicked by the cytoplasmic truncation mutant MT1 Delta C with more robust pro-MMP-2 activation and cell surface expression than wild-type MT1-MMP in transfected cells [5].
• Internalization experiments revealed that MT1-MMP is internalized rapidly in clathrin-coated vesicles whereas MT1 Delta C remains on cell surface [5].
• The level of expression of a transfected metallothionein (MT)-IGcat fusion gene in response to cadmium differed from that of the endogenous MT-IG gene [6].
• OBJECTIVE: To detect the message for membrane type 1 (MT1) matrix metalloproteinase (MMP) in articular cartilage and chondrosarcoma cells, to study its expression in osteoarthritis (OA), and to determine whether interleukin-1beta (IL-1beta) influences its expression [7].
• In both systems, mutations of the TATA box and conserved core of metal responsive element (MRE)a were detrimental to hMT-IG promoter activity suggesting that both elements make significant contributions to hMT-IG transcription [8].

Chemical compound and disease context of MT1G

• Melatonin has been shown to bind to the MT1 G protein-coupled receptor (GPCR) in MCF-7 breast cancer cells to modulate the estrogen response pathway suppressing estrogen-induced estrogen receptor alpha (ERalpha) transcriptional activity, blunting ER/DNA binding activity and suppressing cell proliferation [4].

Biological context of MT1G

• Loss of expression of MT1G and CRABP1 is accompanied by hypermethylation in the 5' regions of these genes, but methylation was not seen in other genes tested [9].
• Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma [9].
• VEGF stimulation also led to the increased acetylation E2F1 as well as the histones in the hMT1G promoter region [10].
• The amino acid sequence encoded by the MT-IF and MT-IG genes differ from the amino acid sequences of the published MT-I proteins at few positions [1].
• Metallothioneins control the bioavailability of zinc and one isoform, MT1G, was reported down-regulated in prostate cancer [2].

Anatomical context of MT1G

• Combined treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza-dC) and the histone deacetylase inhibitor trichostatin A (TSA) resulted in demethylation and re-expression of the MT1G gene in the cell line K2 [9].
• Here, we show that human metallothionein 1G (hMT1G) promoter is upregulated by E2F1 upon VEGF stimulation of human aortic endothelial cells [10].
• The affinities and the functional activities of these ligands were compared with the human receptors (hMT1 or hMT2) expressed in CHO cells as well [11].
• Bmal-1, Per-2, and the melatonin 1 receptor (MT1) showed a robust oscillatory expression in SCN and adrenal gland, whereas a circadian rhythm of dehydroepiandrosterone sulphate was found in plasma [12].
• The MTI-F and MT-IG gene promoters were also functional in human chondrocytes [13].

Associations of MT1G with chemical compounds

• The MT-IF or MT-IG and the MT-IIA genes were regulated in a cell-type specific manner in response to heavy metals and dexamethasone, respectively [3].
• In the presence of Cd2+, MT-IG promoter activity and endogenous mRNA level were, respectively, 4.7- and 3-fold greater than those of MT-IF [14].
• Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors [11].
• Cd(2+) and Zn(2+) induced metallothionein IIa to five times higher levels than metallothionein Ig [15].
• The rate of reaction of NO with these amino acid/proteins was found to be of the order: cysteine > BSA >> MT1, in clear disparity with the size of the reactants [16].

Other interactions of MT1G

• Based on these findings, we conclude that induction of the hMT1G promoter by VEGF and heavy metals occurs through the utilization of different transcription factors [10].
• We can find no previous observation in the literature of metallothionein-1g at both the protein and RNA level in a non-tumour cell, and of metallothionein-0 in a non-fetal cell or tissue [17].
• The human metallothionein (MT)-IG gene (hMT-IG) is tandemly linked in a head-to-head fashion with the hMT-IF gene [18].
• For all 3 HPT isolates, the expression of MT protein and mRNA for the MT-2A, MT-1E, MT-1F and MT-1G isoforms was similar among the isolates and demonstrated no correlation to lethality [19].

Analytical, diagnostic and therapeutic context of MT1G

• E2Fs 1-5 could bind to the hMT1G promoter in a chromatin immunoprecipitation assay [10].
• Furthermore, cell surface biotinylation and indirect immunofluorescence show that transiently expressed MT1-MT4-MMP chimaeras failed to reach the plasma membrane and were retained in the endoplasmic reticulum [20].

References