Disease relevance of MT1A

• One of these genes, hMT-IA, was found to encode a functional protein that confers heavy metal resistance to NIH 3T3 cells after transfer on a bovine papilloma virus-derived vector [1].
• Using normal prostate tissue dissected from glands removed for prostate cancer, it was demonstrated that MT protein expression in the normal prostate is supported by mRNA from the MT-1A, MT-1E, MT-1X, and MT-2A genes [2].
• The finding of different profiles of mRNA expression provides evidence that the MT isoforms may have unique functions and that mRNA for the MT-1A gene could be a potential marker for heavy metal exposure and/or toxicity [3].
• Unlike the hMT-IIA and hMT-IA genes described previously, which are expressed in many different cell types, a high level of expression of the endogenous hMT-IB gene could be detected only in human hepatoma and renal carcinoma cell lines [4].
• In the present study of human invasive breast carcinomas, we examined a correlation between the expression of MT1-, MT2-, and MT3-MMPs, immunolocalization of MT1- and MT2-MMPs, and proMMP-2 activation [5].

Psychiatry related information on MT1A

• The amplification products were also evaluated by Sst-I, Alu-I, Dde-I, and Ita-I restriction enzymes and showed different patterns of digestion reflecting individual differences between the MTC/ IgH junctions [6].

High impact information on MT1A

• Motilin and diabetic gastroparesis: effect of MTC [7].
• 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 [8].
• Internalization experiments revealed that MT1-MMP is internalized rapidly in clathrin-coated vesicles whereas MT1 Delta C remains on cell surface [8].
• 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 [9].
• 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 [9].

Chemical compound and disease context of MT1A

• 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 [10].
• Recombinant (E. coli ) synthesis of mammalian MT1 and MT4 domains as separate peptides in Zn(II) and Cd(II) enriched growth media has rendered metal complexes containing sulfide anions as additional ligands [11].
• As metallothionein proteins play an important antioxidant role, the aim of the present study was to investigate the expression of metallothionein IA (MTIA) and IIA (MTIIA) in HepG2 human hepatoma cells exposed to clofibric acid [12].
• Using in vivo scintigraphy with 111In-pentetreotide, primary tumor localizations were demonstrated in 3/3 carcinoids (2 intestinal carcinoids and 1 lung ACTH-secreting carcinoid; in 2 patients liver metastases larger than 1 cm were visualized), in 1/1 GH-secreting pituitary macroadenoma, and in 1/1 thyroid localization of MTC [13].
• This retrospective investigation was undertaken to clarify the pattern of nodal metastasis in papillary (PTC) and medullary (MTC) thyroid carcinoma [14].

Biological context of MT1A

• 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 [15].
• The levels of gene expression of MT-1A, 1E, 1F, 1G, 1H, and 1X increased, but the level of MT-1B did not increase after exposure to cadmium [16].
• Messenger RNA for the MT-1A gene was detected in 2 of 6 renal samples without correlation to gestational age [17].
• Distinct methylation patterns were further seen in MT1J and MT1A, belonging to the metallothionein gene family [18].
• After exposure to either UV or AFB1, DNA damage was initially repaired faster in the DNA fragments containing the transcribed hMT-IA, hMT-IE, and hMT-IIA genes than in the genome overall [19].

Anatomical context of MT1A

• Tissues selected included liver, motor cortex and cervical cord at C6; MT mRNAs analyzed included MT1A, 1B, 1E, 1F, 1G, 2A, and 3 [20].
• The affinities and the functional activities of these ligands were compared with the human receptors (hMT1 or hMT2) expressed in CHO cells as well [21].
• Membrane-type matrix metalloproteinases-1 and -3 (MT1- and MT3-MMPs) are expressed by activated smooth muscle cells (SMCs) both in vitro and in vivo (19) [22].
• The MT-IIA and the MT-IA genes show a differential response to glucocorticoid hormones and heavy metals, yet they are both expressed in primary human fibroblasts and in HeLa cells [23].
• MT-1A, 1E, 1F and 2A in keloid keratinocytes as compared to normal keratinocytes [24].

Associations of MT1A with chemical compounds

• Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors [21].
• Characterization of expression and stability of recombinant cystein-rich protein human MT1A from yeast [25].
• The goal of this study was to assess the effect of 17beta-estradiol (10 nM) exposure for 1 (E1) or 6 (E6) days on density and function of hMT1 and hMT2 melatonin receptors expressed in Chinese hamster ovary (CHO) cells (CHO-MT1/CHO-MT2 cells) [26].
• The action of MT1 was inhibited by the aliphatic polyamine, spermine, as well as magnesium both at physiological concentrations [27].
• The Zn- and Cd-Clusters of Recombinant Mammalian MT1 and MT4 Metallothionein Domains Include Sulfide Ligands [11].

Other interactions of MT1A

• Treatment with As3+ resulted in a significant increase in the expression of the MT-1X gene and appearance of mRNA for the MT-1A gene [28].
• The increase in MT-1E mRNA appeared to be influenced mainly by exposure to the various metals, whereas the increase in MT-1A mRNA was influenced more by exposure to a metal concentration eliciting a loss of cell viability [29].
• In contrast, mRNAs representing the basal expression of MT-1A and MT-1F were a minor transcript in HPT cells [29].
• The promoters of FLJ45983 and MT1A were methylated above 25% in 18 primary and metastatic tumors [18].

Analytical, diagnostic and therapeutic context of MT1A

• DNA encoding the alpha-domain (106 bp) of the human MT-IA was constructed from chemically synthesized oligomers by repair synthesis and enzymatic ligation, cloned into pUC19 and sequenced [30].
• The localization of MT1 receptor subtype gene expression as determined by in situ hybridization matched the localization of 2-[(125)I]iodomelatonin binding [31].
• The mRNA expression of melatonin receptor subtype MT1 and MT2 were detected by RT-PCR method [32].
• Sequence analysis revealed that there were at least six polymorphisms in the metallothionein-II gene and three in the metallothionein-IA gene [33].
• Northern blot analyses showed that the mRNA expression level of the mta1 gene was 4-fold higher in the highly metastatic cell line MTLn3 than in the nonmetastatic cell line MTC [34].

References