Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the four isoforms of the calcitonin receptor (CTR) described in humans, two differ by the presence of h-CTR1 or absence of h-CTR2 of 16 amino acids in the first intracellular loop. Both receptors are biologically active. The TT cell line derived from a human medullary carcinoma of the thyroid is characterized by the secretion of large amounts of calcitonin. We have recently shown that this cell line expresses h-CTR2. In the present work we have studied the expression of CTR during TT cell proliferation and used dexamethasone to modify calcitonin expression in order to establish if an autocrine regulation involving calcitonin and its receptor was functional in the TT cells. The expression of this receptor and of calcitonin during TT cell proliferation was studied by reverse transcriptase-polymerase chain reaction (RT-PCR). Dexamethasone, a potent inhibitor of TT cell proliferation, levels (day 6 of culture) specifically increased receptor levels from day 8 onwards. CT peptide and CT mRNA levels decreased or were similar during experimental time. CTR regulation by glucocorticoids is suggested in TT cells. Autocrine regulation of CTR is also suggested by relation between CT mRNA levels and CTR mRNA.
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PMID:Calcitonin receptor mRNA expression in TT cells: effect of dexamethasone. 970 72

Down-regulation of copper transporter 1 (CTR1) reduces uptake and sensitivity, whereas down-regulation of CTR2 enhances both. Cisplatin (DDP) triggers the rapid degradation of CTR1 and thus limits its own accumulation. We sought to determine the effect of DDP and copper on the expression of CTR2. Changes in CTR1 and CTR2 mRNA and protein levels in human ovarian carcinoma 2008 cells and ATOX1(+/+) and ATOX1(-/-) mouse embryo fibroblasts in response to exposure to DDP and copper were measured by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and deconvolution microscopy. DDP triggered rapid degradation of CTR1 in 2008 human ovarian cancer cells. However, it increased the expression of CTR2 mRNA and protein levels. Expression of CTR2 was heavily modulated by changes in intracellular copper concentration; copper depletion produced rapid disappearance of CTR2, whereas excess copper increased the level of CTR2 protein. This increase was associated with an increase in CTR2 mRNA and prolongation of the CTR2 half-life. Consistent with prior observations that short hairpin RNA interference-mediated knockdown of CTR2 enhanced DDP uptake and tumor cell kill, reduction of CTR2 by copper starvation also enhanced DDP uptake and cytotoxicity. Comparison of the ability of copper and DDP to modulate the expression of CTR1 in ATOX1(+/+) and ATOX1(-/-) indicated that ATOX1 participates in the regulation of CTR2 expression. Unlike CTR1, the expression of CTR2 is increased rather than decreased by DDP. Therefore, these two copper transporters have opposite effects on DDP sensitivity. CTR2 expression is regulated by copper availability via the copper-dependent regulator ATOX1.
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PMID:Regulation of copper transporter 2 expression by copper and cisplatin in human ovarian carcinoma cells. 2019 31