Disease relevance of MCTS1

• Furthermore, we identified a subset of primary diffuse large B-cell lymphomas that exhibited elevated levels of MCT-1 protein [1].
• Interestingly, all transformed follicular lymphomas in our study demonstrated elevated protein levels of MCT-1 [1].
• There was no detectable MCT-1 protein in leukemic cells from patients with chronic lymphocytic leukemia or in any healthy lymphoid tissue examined [1].
• We demonstrated that there are significantly increased levels of MCT-1 protein in a panel of T-cell lymphoid cell lines and in non-Hodgkin lymphoma cell lines [1].
• We found elevated MCT1 mRNA levels in fresh neuroblastoma biopsy samples that correlated positively with risk of fatal disease and amplification of the "proto-oncogenic" transcription factor MYCN [2].

High impact information on MCTS1

• TMA20 has significant sequence homology with the oncogene MCT-1 [3].
• Lymphoid cell lines overexpressing MCT-1 exhibited increased growth rates and displayed increased protection against apoptosis induced by serum starvation when compared with matched controls [1].
• A novel candidate oncogene, MCT-1, is involved in cell cycle progression [4].
• MCT-1 was localized to the long arm of chromosome Xq22-24 by flourescence in situ hybridization analysis [4].
• Taken together, MCT-1 is a novel candidate oncogene with homology to a protein-protein binding domain of cyclin H [4].

Chemical compound and disease context of MCTS1

• Neuroblastomas produce high amounts of lactic acid and upregulate the H(+)-linked monocarboxylate transporter isoform 1 (MCT1/SLC16A1) [2].
• The H+-Linked Monocarboxylate Transporter (MCT1/SLC16A1): A Potential Therapeutic Target for High-Risk Neuroblastoma [2].

Biological context of MCTS1

• Expression of the candidate MCT-1 oncogene in B- and T-cell lymphoid malignancies [1].
• Both cyclin D1 and MCT-1 are involved in regulating passage of cells through the G1 phase of the cell cycle [5].
• The MCT-1 promoter is TATA-less with a consensus initiator element located at the transcription start site and facilitated by two Sp1 sites that directs basal transcription [6].
• This 26-mer oligonucleotide containing the LMBF binding site is required for maximum transcriptional activity of the MCT-1 promoter [6].
• Cloning and characterization of the promoter region for the MCT-1 oncogene is described [6].

Anatomical context of MCTS1

• MCT-1 has been shown to decrease cell-doubling time, dramatically shortening the duration of G(1) transit time and/or G1-S transition, and transforms NIH3T3 fibroblasts [5].
• Furthermore, MCT-1 is capable of transforming immortalized human mammary epithelial cells and promoting genomic instability [7].
• A model system for the study of human retinal angiogenesis: activation of monocytes and endothelial cells and the association with the expression of the monocarboxylate transporter type 1 (MCT-1) [8].
• In the subjects with rhinitis, seasonal submucosal CD3+ counts correlated with MBP+ eosinophils (r = 0.56; p less than 0.05) and MCTS (r = 0.65; p less than 0.02) [9].
• The lactate-sensitive part of fluorescein transport was completely blocked by p-chloromercuribenzenesulfonic acid (pCMBS), a specific inhibitor of the monocarboxylate transporter-1 (MCT-1) that by Western blotting and immunofluorescence was identified in mitochondria of HT-29 cells [10].

Associations of MCTS1 with chemical compounds

• We have previously described a novel series of potent blockers of the monocarboxylate transporter, MCT1, which show potent immunomodulatory activity in an assay measuring inhibition of PMA/ionomycin-induced human PBMC proliferation [11].
• In contrast, alpha-cyano-4-hydroxycinnamate, phloretin, l-lactate, beta-hydroxybutyrate, butyrate, and pyruvate, inhibitors and substrates of monocarboxylate transporter 1 (MCT1), significantly reduced DL-HMB uptake [12].
• The transcription initiation site in the MCT1 promoter was identified as a guanine nucleotide 281 bp upstream from the translation initiation site and is surrounded by a guanine-cytosine-rich area [13].
• In conclusion, the methionine hydroxy analogue is transported in Caco-2 cell apical membrane by a transport mechanism with functional characteristics similar to those of MCT1 [12].
• The uptake of GHB in rat MCT1 gene-transfected MDA-MB231 cells was significantly decreased in the presence of the flavonoids apigenin, biochanin A, chrysin, diosemin, fisetin, genistein, hesperitin, kaempferol, luteolin, morin, narigenin, phloretin, and quercetin, but was not affected by the flavonoid glycosides phloridzin and rutin [14].

Regulatory relationships of MCTS1

• Forced expression of MCT-1 significantly increases the number of DNA damage-induced foci involving gamma-H2AX and 53BP1 [7].
• The phosphorylation of genomic stabilizers H2AX and NBS1 are enhanced in MCT-1-overexpressing cells [7].

Other interactions of MCTS1

• This relationship between MCT-1 and cyclin H implied a potential role for MCT-1 in cell cycle regulation [4].
• Constitutive expression of MCT-1 results in a strong proliferative signal and is associated with deregulation of protein kinase-mediated G1/S phase checkpoints [5].
• Knockdown of endogenous MCT-1 using an siRNA approach attenuates the H2AX phosphorylation and the G1/S checkpoint defect [7].

Analytical, diagnostic and therapeutic context of MCTS1

• Using mobility shift assays with a 26-mer oligonucleotide, which contains this fragment and its flanking regions, we demonstrated the presence of sequence-specific DNA-binding protein in both Jurkat and Hela nuclear extracts that we designated as LMBF (for lymphoid MCT-1 binding factor) [6].
• MCT-1 maximal velocity increased in the rHuEPO group (P < 0.05), reaching higher values than in the placebo group (P < 0.05) after treatment [15].
• Development of MCTS technique for 3-PM liquid scintillation counting [16].

References