Disease relevance of MT1E

• These results suggest a possible relationship between estrogen receptor status and MT-1E gene expression in human breast cancer [1].
• Although the MTD was not reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies because it is the dose determined from studies in metastatic patients with no toxicity when given concurrently with radiation [2].
• RESULTS: In conjunction with docetaxel 75 mg/m(2) every 4 weeks, the MTD of Doxil was 30 mg/m(2) and required granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia [3].
• 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 [4].
• A decrease in polyp numbers could not be demonstrated, but the trend toward increased apoptosis at the MTD and the observation of mucinous change histologically suggest that further investigation of drugs of this class might be warranted [5].

High impact information on MT1E

• 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 [6].
• Internalization experiments revealed that MT1-MMP is internalized rapidly in clathrin-coated vesicles whereas MT1 Delta C remains on cell surface [6].
• In celery plants, MTD activity and tissue mannitol concentration are inversely related [7].
• Treatment of celery cells with salicylic acid resulted in increased MTD activity and RNA [7].
• In one cell line that failed to express detectable amounts of hMT-IE, treatment with the demethylating agent 5-azacytidine led to cadmium-inducible expression of this subtype [8].

Chemical compound and disease context of MT1E

• The MT-1E isoform was found to be present in estrogen receptor-negative breast cancer cell lines (MDA-MB-231 and Hs578T) but not detectable in the estrogen receptor-positive cell lines (T47D, MCF7, and ZR75-1 cells) [9].
• 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].
• The MTD of cinchonine administered by continuous i.v. infusion was 30 mg/kg/d. Prolonged cardiac repolarization was the main dose-limiting toxicity [11].
• INTRODUCTION: This was a dose escalation phase I trial designed to establish the MTD (maximum tolerated dose) and toxicity profile of the combination of gemcitabine, leucovorin and 5-fluorouracil (5-FU) [12].
• PURPOSE: The objective of this study was to determine the docetaxel MTD when combined with gemcitabine or vinorelbine in advanced breast cancer patients who had received previous anthracycline-based chemotherapy for advanced disease [13].

Biological context of MT1E

• There was a sex difference (P < 0.05). in basal gene expression of MT-1E [14].
• Metallothionein-1 was shown to consist of a mixture of isoforms, confirmed as metallothionein-1e, metallothionein-1g and metallothionein-1l by comparison with cDNA sequences obtained by screening a human monocyte cDNA library [15].
• 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 [16].
• 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 [17].
• At sublethal doses, the rate of tumor response (cures +/- complete responses + partial responses) increased with increasing dose: 4.1 MBq, 27%; 5.9 MBq, 41%; 8.5 MBq, 69%; and 9.6 MBq, 79% (maximum tolerated dose, MTD) [18].

Anatomical context of MT1E

• The cellular content of MT protein was also shown to be elevated in the estrogen-receptor-negative cell lines that express MT-1E mRNA [1].
• The affinities and the functional activities of these ligands were compared with the human receptors (hMT1 or hMT2) expressed in CHO cells as well [19].
• Myelotoxicity was dose-limiting; bone marrow transplantation allowed for an increase of the MTD to 400 microCi of 131I-17-1A, whereas the MTD of 125I-17-1A with bone marrow support had not been reached at 5 mCi [20].
• 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 [21].
• The effect of thyroid replacement therapy (TRT) was evaluated in 372 children with minimal thyroid dysfunction (MTD; augmented TSH response to TRH, deficient iodine consumption, goiter, short stature and retarded bone age), by comparison of pre- with post-observation height in periods of 6 months with and without TRT alternated [22].

Associations of MT1E with chemical compounds

• It was shown that acute exposure to either As(3+) or Cd(2+) increased the levels of mRNAs for the MT-1E, MT-1X, and MT-2A genes, whereas extended exposure only increased these mRNAs following exposure to Cd(2+) [23].
• Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors [19].
• A mannitol catabolic enzyme that oxidizes mannitol to mannose (mannitol dehydrogenase, MTD) has been identified [7].
• Tandutinib at the MTD (525 mg twice daily) should be evaluated more extensively in patients with AML with FLT3-ITD mutations to better define its antileukemic activity [24].
• Without G-CSF, the MTD was docetaxel 60 mg/m(2) and Doxil 30 mg/m(2) every 3 weeks; only 1 (7%) out of 15 patients treated at this dose level had cycle 1 DLT [3].

Other interactions of MT1E

• 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 [25].
• Differential expression of the MT-1E gene in estrogen-receptor-positive and -negative human breast cancer cell lines [1].
• CONCLUSIONS: MT protein in the normal human prostate is supported by transcription of mRNA from the MT-1A, MT-1E, MT-1X, and MT-2A genes [26].
• Increased expression of MT-1E, as well as MT-1X and MT-2A, protects against metal toxicity in PMC42 breast cancer cells [27].
• RESULTS: PC-3 cells that overexpress the MT-3 gene are growth inhibited compared with either untransfected cells, cells with blank vector, or cells with similar overexpression of the MT-1E gene [28].

Analytical, diagnostic and therapeutic context of MT1E

• In this study, data on MT-2A, MT-1E, MT-1F mRNA analysis via reverse transcription-polymerase chain reaction in invasive ductal breast cancer tissues and their adjacent benign breast tissues from 27 mastectomies are presented [29].
• The mRNA expression of melatonin receptor subtype MT1 and MT2 were detected by RT-PCR method [30].
• In nude mouse xenograft studies, 27 reduced PSA levels by 95% and tumor weight by 87% at a dose below its MTD [31].
• In nude mouse xenograft studies, 5 reduced circulating PSA levels by 99% and tumor weight by 85% at a dose just below its MTD [32].
• The MTD for post-RT chemotherapy was 375 mg/m2; therefore, the recommended dose of 5-FU is 325 mg/m2 [33].

References