Disease relevance of MT2A

• In this study, expression levels of the 8 known MT-1 and MT-2 functional isoforms in human invasive ductal breast cancer specimens were determined by RT-PCR [1].
• The expression of MT-1 and MT-2 isoform-specific mRNA varied among three commonly utilized prostate cancer cell lines [2].
• Immunohistochemical analysis disclosed no immunoreactivity for MT-1 and MT-2 (designated as MT-1/2 to reflect the nonspecificity of the antibody for the two isoforms) in cells comprising the normal bladder or in nonmalignant bladder disorders, such as cystitis and interstitial cystitis [3].
• Expression of metallothionein II in intestinal metaplasia, dysplasia, and gastric cancer [4].
• Expression of human metallothionein-II fusion protein in Escherichia coli [5].

Psychiatry related information on MT2A

• Metallothionein 2A promoter (MT2A) was induced throughout the study time at high SM concentration [6].
• The analytical procedure developed has been used for the first time in comparative studies of the distributions of MT-1, MT-2, and MT-3 in brain samples taken from patients with Alzheimer's disease and from a control group [7].
• Ramelteon (TAK-375), a selective MT1/MT2-receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment [8].
• Two of these analogs, a linear peptide, melanotan I, and a cyclic truncated peptide, melanotan II (MTI and MTII, respectively) have been patented and tested clinically for studies on tanning of the skin (MTI) and for diagnosis and treatment of male erectile dysfunction (MTII) [9].
• Pharmacological or genetic disruption of IL-1 receptor signaling prevented MTII-mediated reductions in locomotor activity, but did not reduce MTII-induced anorexia [10].

High impact information on MT2A

• MTs exist in several molecular forms (MT-I, MT-II) and are encoded by a multi-gene family containing at least 14 closely related genes and pseudogenes [11].
• We now show that the rate of transcription of MT2A is the same on treatment with interferon or dexamethasone, but that the mRNA accumulates much faster with dexamethasone, indicating that post-transcriptional events are important in the latter case [12].
• Furthermore, comparison of regions upstream of the MT2A gene, two HLA genes and one HLA class II gene reveals a homologous sequence of approximately 30 base pairs (bp) which may be involved in regulating transcription of interferon-induced genes [12].
• We now show that IFN-alpha treatment results in a three- to fivefold increase in the transcription of MT2 and HLA class I genes in human T98G neuroblastoma cells [12].
• One is a functional metallothionein-II gene, the other a pseudogene, lacking introns, terminating in a poly(A) tail and flanked by two direct repeats [13].

Chemical compound and disease context of MT2A

• We previously demonstrated that Actinomycin D (ActD) enhanced HIV-1 replication in the MT-2 cell, a human T-cell leukemia virus type-1-infected cell line [14].
• Treatment of the human metastatic breast cancer cell line MT-2 with oltipraz results in a concentration-dependent increase in the activity of the calcium-dependent calpain, as measured towards the BOC-LM-CMAC fluorescent substrate [15].
• Conditioned media from cultures of human T-cell lymphotropic virus type I-infected cell line (MT-2) as well as peripheral lymphocytes from a hypercalcemic ATLL patient stimulated cyclic AMP production in osteoblast-like rat osteogenic sarcoma cells (UMR 106) and bone resportion in organ cultures of fetal mouse calvaria [16].
• An HIV-1 strain carrying a shorter form of the transmembrane glycoprotein (TM) with a mobility of 32 kD, named KB-1, was isolated from a Japanese male hemophiliac by coculture of his peripheral blood mononuclear cells (PBMCs) with MT-2 cells and adaption to TALL-1 cells [17].
• Infection of the human T-cell line MT-2 with EBV recombinants that had a hygromycin resistance gene and subsequent selection with this drug permitted isolation and long-term maintenance of EBV-infected MT-2 clones [18].

Biological context of MT2A

• When we used antisense MT2A to interdict the effect of MT2A, the inhibition of cell proliferation and induction of apoptosis were significantly enhanced [19].
• Our data suggest that the physical interaction of EOLA1 and MT2A may have an important role of cell protection in inflammation reaction [20].
• Using the EOLA1 cDNA as bait, we performed a yeast two-hybrid screening of a human liver cDNA library and identified metallothionein 2A (MT2A) as associated protein [20].
• Our results are in support of the protective role against oxidative stress ascribed to MTs and provide evidence that MT2A expression may be a beneficial downstream adaptive response in complex I-deficient cells [21].
• Using human-mouse cell hybrids and hybridization probes derived from cloned and functional human MT1 and MT2 genes, we show that the functional human genes are clustered on human chromosome 16 [22].

Anatomical context of MT2A

• We conclude that MT2A offers significant protection against the main death-causing consequences of rotenone-induced complex I deficiency in HeLa cells [21].
• Analysis of RNA from somatic cell hybrids indicated that hybrids that contained human chromosome 16 expressed both human MT1 and MT2 mRNA, and this expression is regulated by both heavy metal ions and glucocorticoid hormones [22].
• The affinities and the functional activities of these ligands were compared with the human receptors (hMT1 or hMT2) expressed in CHO cells as well [23].
• When transfected into HTLV-I-infected T-cell lines MT-2 and HUT-102, IL-6 promoter/CAT plasmids were strongly activated without any stimulation [24].
• In the CNS, MT-I and MT-II are conspicuously absent from neuronal populations, yet abundant in fibrous and protoplasmic astrocytes [25].

Associations of MT2A with chemical compounds

• Expression of MT2A (MT isoform 2A), but not MT1A or MT1B RNA, was significantly inducible by rotenone (up to 7-fold), t-BHP (t-butyl hydroperoxide; 5-fold) and CdCl2 (50-fold), but not ZnCl2 [21].
• Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors [23].
• The results showed that transient overexpression of human MT1A, MT2 and MT3 genes dynamically affected cell viability, and the effect was influenced by zinc and cadmium ions [26].
• Preincubation overnight with 150 microM zinc sulfate or 5 microM cadmium chloride induced a 20- to 30-fold increase of MT2A mRNA; high levels of MT2A mRNA were maintained during the subsequent challenge period with AA, even after the zinc was removed [27].
• Purified GIF is a 68 amino acid small protein, and its amino acid sequence is 70% identical to that of human metallothionein II with a 1 amino acid insert and a unique 6 amino acid insert in the NH2-terminal and the COOH-terminal portions, respectively [28].

Physical interactions of MT2A

• Metallothionein 2A interacts with the kinase domain of PKCmu in prostate cancer [29].
• Results demonstrate that MT-3 binds Zn2+ and Cd2+ ions more weakly than MT-2 but exposes higher metal-binding capacity and plasticity [30].

Regulatory relationships of MT2A

• These cocultured FRTL-5 cells with MT-2 cells expressed IL-6 mRNA and proliferated more actively than those cocultured with CCRF-CEM cells [31].
• These results suggested that TNF and IFN-beta activate MT-II gene expression by partially distinct mechanisms [32].

Other interactions of MT2A

• Because metallothioneins are associated with cell proliferation and CR, the PKCmu-MT 2A interaction may contribute to CR and/or AI in PC [29].
• Metal binding of metallothionein-3 versus metallothionein-2: lower affinity and higher plasticity [30].
• The goals of this study were to determine the expression of metallothionein isoform 1 and 2 proteins (MT-1 and MT-2) in bladder cancer and then to determine which MT isoform-specific genes promoted the expression of these proteins [3].
• Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibroblasts, and no differences could be found between the lining and sublining [33].
• In particular, CDC20 and MT2A represent a potential biomarker of human gastric cancer [34].

Analytical, diagnostic and therapeutic context of MT2A

• ECRG2 co-localized with MT2A mostly to nuclei and slightly to cytoplasm, as shown by confocal microscopy [19].
• In the co-transfection of ECRG2 and MT2A assays, cell proliferation was inhibited and apoptosis was slightly induced compared with control groups [19].
• The maximum molar ratio of arsenic to hMT-2 was found to be more than 6:1 on ICP-AES, UV absorption spectroscopy and MALDI-TOF-MS [35].
• This new polyclonal antibody recognized recombinant MT2A protein in western blot analysis [36].
• A detailed sequence analysis showed that 10 of 16 genes were high homologous to genes known in GenBank, such as RPL31, S100 A2, MT2A, etc [37].

References