Disease relevance of TAAR1

• Additionally, a large number of thyroamine derivatives were synthesized in an effort to understand the molecular basis of TAAR1 activation and hypothermia induction [1].
• In lymph node-positive patients a trend between high TA1 reactivity and a worse overall survival was also noted (log rank P = 0.128; Wilcoxon P = 0.054), with a 6-year survival of 42% in the strongly reactive tumors (n = 16) and 65% in the negative to weakly reactive carcinomas (n = 105) [2].
• Heterogeneous staining was found in villous adenomas with focal intramucosal adenocarcinoma but was negative in tubular adenomas, suggesting that expression of TA1/E16 may correlate with neoplastic progression in the colon [3].
• Requirements for TA1-induced internalization of c-erbB-2 have been studied using the SKBr3 human breast cancer cell line and several rat fibroblast cell lines that express either wild-type or mutant human c-erbB-2 [4].
• The TAR element of HIV-2 (TAR-2) resembles a tandem duplication of the TAR-1 hairpin structure [5].

Psychiatry related information on TAAR1

• A family-based and case-control association study of trace amine receptor genes on chromosome 6q23 in bipolar affective disorder [6].

High impact information on TAAR1

• We have previously shown that agents capable of activating protein kinase C (PKC), such as FGF and the phorbol ester tetradecanoyl phorbol-13-acetate (TPA), inhibit the differentiation of the adipogenic cell line TA1, as measured by the rapid loss of adipocyte-specific RNAs [7].
• We report here that the treatment of fully differentiated TA1 adipocytes with FGF at 10 ng/ml induces the reversal of adipocyte differentiation, even in cells where PKC activity has been down-regulated by TPA pretreatment [7].
• Therefore, we propose that there are two FGF-sensitive pathways in TA1 cells: one responsible for the initiation of differentiation (TPA sensitive) and another required for maintenance of the adipose phenotype (TPA insensitive) [7].
• When the normally positioned TAR element (TAR-1) is inactivated by mutations in either the Tat binding site or the apical loop sequence, which acts as the binding site for a cellular factor, transactivation can be rescued by a wild-type TAR element placed downstream (TAR-2) [8].
• Previous reports from this laboratory have shown that the first peak (PI) is serologically the same as a group of trophoblast membrane antigens tentatively designated as TA1 [9].

Chemical compound and disease context of TAAR1

• CONCLUSIONS: The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity [10].
• A phase II study was performed to evaluate the clinical and immunological effects of a regimen of cisplatin (DDP) and etoposide (VP-16) combined with thymosin-alpha 1 (TA1) and low-dose interferon-alpha 2a (IFN) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) [11].

Biological context of TAAR1

• We have found that agents that are capable of activating protein kinase C, such as basic fibroblast growth factor and phorbol esters, inhibit the differentiation of the adipogenic cell line TA1 without stimulating cell growth [12].
• We investigated the possibility that the difference in brain size between men and women is reflected in differences in the numerical density of neurons in area TA1, an area associated with morphologic and psychological sex differences [13].
• Slightly more rapid internalization of TA1 was observed in rat cells that expressed c-erbB-2 with a single point mutation in the transmembrane domain [4].
• A murine monoclonal antibody, TA1, is directed against an epitope on the extracellular domain of the HER-2/neu (c-erbB-2) gene product [4].
• The peptides encoded by the rat liver oncofetal cDNA TA1 and the human lymphocyte activation gene E16 display a high degree of homology with coding regions recently identified in Schistosoma mansoni and Caenorhabditis elegans [3].

Anatomical context of TAAR1

• For comparison, the rat TAAR1 receptor was expressed in the AV12-664 cell line [14].
• We have previously shown that TA1 is a lymphocyte product of allogeneic responses, and the present results indicate that P1 proteins are themselves involved in the biology of lymphocyte responses to allogeneic cells [9].
• Similar rates of internalization of TA1 were observed in SKBr3 and in rat fibroblasts that expressed human c-erbB-2 [4].
• TA1/E16 message also was detected in adenocarcinomas from breast, endometrium, salivary gland, and esophagus [3].
• Two of the five cervical cancer cell lines, HTB31 (C-33A) and 32 (HT-3), harbored missense mutations in codons 273 and 245 respectively, whereas the other three tumor cell lines, HTB33 (ME180), 34 (MS751) and 35 (SIHA), did not reveal any mutation in the p53 coding sequence spanning codons 126-307 [15].

Associations of TAAR1 with chemical compounds

• Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor [16].
• In addition, TAAR1 effects on dopamine uptake could be blocked by a protein kinase A or protein kinase C (PKC) inhibitor [17].
• Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor activated by a broad range of monoamines and amphetamine-related psychostimulants [17].
• Taken together, this study provides evidence that TAAR1 is involved in functional regulation of DAT and suggests that TAAR1 is a potentially important target for therapeutics for methamphetamine addiction [17].
• Cytoarchitectonic area TA1 (von Economo) in the cortex of the planum temporale within the Sylvian fissure, which is auditory association cortex and documented to be part of the neural substrate of language functions, was studied quantitatively in the brain specimens of five women and four men (mean age of 50 year) [13].

Other interactions of TAAR1

• Recent study of linkage disequilibrium mapping showed one of the trace amine receptor (TRAR) genes, TRAR4, was associated with schizophrenia [18].
• The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems [19].

Analytical, diagnostic and therapeutic context of TAAR1

• For T3, T4 patients, strong TA1 immunoreactivity correlated with a shortened disease-free survival (log rank P = 0.0018; Wilcoxon p = 0.0078) and overall survival (log rank P = 0.0002; Wilcoxon P = 0.0013) [2].
• Western blot analysis using antibodies against TA1/E16-deduced peptides identified major reactive bands of approximately 35 and 19 kDa in neoplasms but not in normal tissue [3].
• Steady-state TA1/E16 mRNA levels varied considerably between carcinomas and did not correlate simply with mitotic index, modified Dukes' stage, or tumor size [3].
• The immunohistochemical method using TA1 monoclonal antibody for p185 was exquisitely sensitive in acetone-fixed frozen sections and provided an excellent approach for judging overexpression as confirmed by the various molecular analyses [20].
• PATIENTS AND METHODS: Forty-six patients with measurable metastatic melanoma were treated with DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by continuous intravenous infusion on days 8 to 12 [10].

References