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

The cadherins are a family of calcium-binding membrane glycoproteins. Most cadherins are capable of acting as cell adhesion molecules (CAMs). In order to begin a thorough analysis of the roles of these CAMs in the testis, we employed a reverse transcriptase-polymerase chain reaction (RT-PCR) strategy to identify the cadherins expressed in this tissue at various stages of development. Oligonucleotides encoding amino acid sequences that are conserved among all of the known cadherins were used as primers in the RT-PCR, with cDNA preparations of fetal, newborn, 7-day, 21-day, and adult mouse testes employed as templates. The PCR products were subcloned into a plasmid vector and sequenced. On the basis of the nucleotide sequences of these PCR products, we have determined that five previously characterized cadherins (E-cadherin, N-cadherin, P-cadherin, K-cadherin, and OB-cadherin), as well as two novel cadherins (T1-cadherin and T2-cadherin), are expressed at various stages during testicular development. In order to determine the expression patterns of these cadherins, we ascertained the mRNA levels of each cadherin normalized to the levels of hypoxanthine phosphoribosyltransferase mRNA in fetal, newborn, 7-day, 21-day, and adult mouse testes. We observed that N-cadherin mRNA is expressed at all stages of testicular development, with maximal levels being present in the testes of 21-day-old mice. Furthermore, we found that E-, P-, K-, OB-, and T2-cadherin mRNAs are all expressed in the fetal gonad. The testicular levels of these cadherin mRNAs decreased dramatically after birth. Conversely, T1-cadherin mRNA was not detected in the fetal, newborn, and 7-day-old testes but was present in 21-day-old and adult testes. T1-cadherin levels were 10-fold higher in the testes of adult mice, compared to the levels found in the testes of 21-day-old mice. We speculate that these cadherins will be found to be intimately involved in mediating cell interactions during testicular development.
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PMID:A comprehensive survey of the cadherins expressed in the testes of fetal, immature, and adult mice utilizing the polymerase chain reaction. 887 95

Coumarins are a large family of compounds derived from a wide range of plants, fungi, and bacteria, and coumarin derivatives can have extremely variable structures and consequently diverse biological properties including antitumor activity. Compounds that bear a benzimidazole moiety are known to possess antitumor activity and a variety of other biological activities. High-throughput screening of a compound library identified a coumarin-containing and a benzimidazole-containing compound [#32, 7-(diethylamino)-3-(1-methyl-1H-benzimidazol-2-yl)-2H-chromen-2-one] that has potent anticancer activity. Evaluation of 17 additional analogs further identified three compounds with anticancer activity in 14 different human cancer cell lines. Fluorescence-activated cell sorting and western blotting analyses suggested that these compounds can induce caspase-dependent apoptosis. Real-time reverse transcriptase PCR analyses of 26 cancer-related genes revealed that seven genes (NPPB, ATF3, DDIT4, CDH10, TSPAN14, TXNIP, and AXL) were significantly upregulated and nine genes (PAGE4, LRP8, SNCAIP, IGFBP5, SLCO2A1, CLDN2, ESRRG, D2HGDH, and PDGFRA) were significantly downregulated. The most upregulated gene is natriuretic peptide precursor B (NPPB) or brain natriuretic peptide, which is increased by 7-, 27-, and 197-fold at 12, 24, and 48 h, respectively. The second most upregulated gene is ATF3, which is increased by 23-fold at the 48 h timepoint. PAGE4 and IGFBP5 are the two most downregulated genes, with a 17-fold reduction in both genes. The expression of several genes (DDIT4, PDGFRA, LRP8, IGFBP5) and western blotting data on key signaling proteins indicate that compound #32 significantly inhibits the PI3K-AKT-mTOR pathway, an intracellular signaling pathway critical in cell proliferation and apoptosis.
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PMID:Derivatives containing both coumarin and benzimidazole potently induce caspase-dependent apoptosis of cancer cells through inhibition of PI3K-AKT-mTOR signaling. 2581 64