Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

cDNA clones for calretinin, a member of the troponin-C family of calcium-binding proteins, were isolated from a cDNA library of the human colon carcinoma cell line WiDr. Sequence analysis revealed two forms of alternatively spliced calretinin mRNAs encoding C-terminally truncated proteins. Exon 7 was either spliced to exon 9 (delta 8) or to exon 10 (delta 8,9); both resulted in a frame shift and a translational stop at the second codon of exon 9 (delta 8), or at codon 15 of exon 10 (delta 8,9), respectively. The presence of delta 8 and delta 8,9 calretinin mRNA in WiDr cells was confirmed using reverse-transcriptase PCR and sequence analysis of the amplicon, as well as by a ribonuclease protection assay. Co115/3 and three other human colon carcinoma cell lines were found, by reverse-transcriptase PCR to also contain delta 8,9 calretinin mRNA. The truncated proteins were able to bind calcium, as evidenced by a calcium blot of the delta 8 form (calretinin-20k) and delta 8,9 form (calretinin-22k) expressed in Escherichia coli. Immunohistochemical staining using an antiserum specific for the novel C-terminus of calretinin-22k confirmed its presence in WiDr, Co115/3 and three additional colon carcinoma cell lines. The fact that alternative splicing of calretinin was found in five different cell lines suggests that alternatively spliced calretinins fulfill a physiological function.
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PMID:Alternative splicing of calretinin mRNA leads to different forms of calretinin. 760 11

It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol-rich low-density lipoprotein (LDL) particles. In a prospective study of 25 patients with colorectal carcinoma, we measured intraindividual shifts in serum cholesterol levels after surgery, and the expression of LDL-receptor mRNA in surgically removed specimens. A significant rise in plasma cholesterol levels was observed in patients 3 and 12 months after curative surgery, but not after non-curative surgery. In human colon carcinoma tissues LDL receptor mRNA expression, as determined by competitive reverse-transcriptase-polymerase-chain reaction, was found to be significantly increased when compared to tissues from the tumour-free margin (median values, 1.2 x 10(6) vs. 2.0 x 10(5) molecules/micrograms total cellular RNA, respectively, n = 17). The extent of LDL-receptor mRNA expression positively correlated to the percentage rise of plasma cholesterol levels 3 months (n = 7, r = 0.8763) and 12 months (n = 6, r = 0.9181) after curative surgery. This finding provides in vivo evidence that the tumour tissue itself contributes to decreased plasma cholesterol levels in patients suffering from colorectal carcinomas. It supports the hypothesis that low cholesterol levels in cancer patients are a consequence, and not the cause, of the malignancy.
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PMID:Increased LDL receptor mRNA expression in colon cancer is correlated with a rise in plasma cholesterol levels after curative surgery. 775 50

Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix-degrading metalloproteinases that are believed to contribute to the complex process of cancer invasion and metastasis. The secretion level of MMP-7 as assayed by immunoblot analysis was low but distinct in the culture medium of a human colon carcinoma cell line, WIDr, whereas none of the fibroblasts secreted the detectable level of MMP-7. The coculture of WiDr with various human fibroblasts from orthotopic (colon) and ectopic (thyroid, brain, lung, and skin) organs significantly stimulated the secretion of MMP-7 compared with the cultures of individual cells. Reverse transcriptase-polymerase chain reaction analysis and RNA blot analysis suggested that this enhancement occurred at a pretranslational level. The extent of the stimulation was widely varied by the fibroblasts used and was dependent on the cellular ratios and density in the coculture. There may exist a tendency that fibroblasts of orthotopic origin stimulate more extensively than do those of ectopic origin. Moreover, in the coculture of high cell density, normal fibroblasts from the ectopic organs reduced the MMP-7 secretion. The stimulation of MMP-7 secretion may be partially mediated through soluble factor(s); however, direct cell-cell interactions would be required for maximum stimulation. The enhanced MMP-7 secretion was also observed in coculture of colon fibroblasts with other colorectal carcinoma cell lines such as RCM-1 and SW837, which secreted hardly detectable levels of MMP-7 in the individual culture. These results suggest that MMP-7 secretion by colon carcinoma cells is influenced by specific interactions between the carcinoma cells and host fibroblasts.
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PMID:Modulation of matrix metalloproteinase-7 (matrilysin) secretion in coculture of human colon carcinoma cells with fibroblasts from orthotopic and ectopic organs. 922 Apr 95

We studied the beta-1,3-galactosyltransferase (GalT) and alpha-1,2-fucosyltansferase (FT) involved in the biosynthesis of type-1-chain carbohydrate antigens in human colon adenocarcinoma cell lines. We detected a GalT activity able to use GlcNAc as acceptor and found that lacto-N-biose I (Galbeta1-3GlcNAc) is the only reaction product. Such beta1,3GalT is kinetically similar to a pig trachea enzyme involved in mucin synthesis. The specific activity is high in cells that react strongly with anti-Lewis a and anti-Lewis b antibodies, and undetectable in a cell line that lacks antibody reaction. Reverse-transcriptase-mediated PCR analysis followed by DNA sequencing indicated that secretor-type alpha1,2FT is expressed in the cells, while the H type alpha1,2FT is not. The apparent Km values for donor and acceptor substrates determined for alpha1,2FT are similar to those of secretor-type alpha1,2FT and the specific activity measured correlates with Lewis b antigen expression on the cell surface. Moreover, some of the cell lines express Lewis y and H type 2 antigens, indicating that secretor type alpha1,2FT is responsible for their synthesis. Results suggest that biosynthesis of type-1-chain tumor-associated antigens in human colon carcinoma cells is operated by secretor-type alpha1,2FT, as reported in normal mucosa, and that beta1,3GalT activity may play a relevant role in its control.
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PMID:Beta-1,3-galactosyltransferase and alpha-1,2-fucosyltransferase involved in the biosynthesis of type-1-chain carbohydrate antigens in human colon adenocarcinoma cell lines. 976 Jan 91

ADAMTS (A Disintegrin And Metalloproteinase domain, with ThromboSpondin type-1 modules) is a recently described family of zinc-dependent proteases which play important roles in a variety of normal and pathological conditions, including arthritis and cancer. In this work, we report the identification and cloning of cDNAs encoding seven new human ADAMTSs. These novel enzymes have been called ADAMTS-13, -14, -15, -16, -17, -18, and -19. All of them show a domain organization similar to that of previously characterized family members, consisting of a signal sequence, a propeptide, a metalloproteinase domain, a disintegrin-like domain, a cysteine-rich region, and a variable number of TS-1 repeats. Expression analysis revealed that these ADAMTS genes are mainly expressed in fetal tissues, especially in lung (ADAMTS14, ADAMTS16, ADAMTS17, ADAMTS18, and ADAMTS19), kidney (ADAMTS14, ADAMTS15, and ADAMTS16), and liver (ADAMTS13, ADAMTS15 and ADAMTS18). Reverse transcriptase--polymerase chain reaction analysis also revealed the expression of some of these new ADAMTSs in different human adult tissues, such as prostate (ADAMTS13, ADAMTS17, and ADAMTS18), and brain (ADAMTS13, ADAMTS16, ADAMTS17, and ADAMTS18). High levels of ADAMTSs transcripts were also observed in some tumor biopsies and cells lines, including osteosarcomas (ADAMTS19), melanoma and colon carcinoma cells (ADAMTS13). Chromosomal location analysis indicated that the seven identified ADAMTS genes are dispersed in the human genome mapping to 9q34, 10q21, 11q25, 5p15, 15q24, 16q23, and 5q31, respectively. According to these results, together with a comparative analysis of ADAMTSs in other eukaryotic organisms, we conclude that these enzymes, with at least 18 distinct members encoded within the human genome, represent an example of a widely expanded protease family during metazoan evolution.
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PMID:Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains. 1186 12

Transforming growth factor-beta1-stimulated clone 22 (TSC-22) encodes a leucine zipper-containing protein that is highly conserved among various species. Mammalian TSC-22 is a potential tumor suppressor gene. It translocates into nuclei and suppresses cell division upon antiproliferative stimuli. In human colon carcinoma cells, TSC-22 inhibits cell growth by upregulating expression of the p21 gene, a cyclin-dependent kinase (Cdk) inhibitor. We previously showed that the Xenopus laevis homologue of the TSC-22 gene (XTSC-22) is required for cell movement during gastrulation through cell cycle regulation. In this report, we investigated the molecular mechanism of the antiproliferative effect of XTSC-22. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis suggested that XTSC-22 did not affect the expression levels of the p21 family of Cdk inhibitors or other cell cycle regulators. Analysis of deletion mutants of XTSC-22 revealed that nuclear localization of the N-terminal TSC-box is necessary for cell cycle inhibition by XTSC-22. Further experiments suggested that p27Xic1, a key Cdk inhibitor in Xenopus, interacts with XTSC-22. Because p27Xic1 is a cell cycle inhibitor with a nuclear localization signal, it is possible that XTSC-22 suppresses cell division by translocating into the nucleus with p27Xic1, where it may potentiate the intranuclear action of p27Xic1.
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PMID:TSC-box is essential for the nuclear localization and antiproliferative effect of XTSC-22. 1739 98

Reverse transcriptase (RT) inhibitors are emerging as a novel class of anticancer differentiating agents, active in several human tumor cell models, such as melanoma and prostate, thyroid and colon carcinoma. Indeed, much evidence suggests that they may act by inhibiting endogenous RT, a gene highly expressed in undifferentiated and transformed cells. We therefore evaluated whether endogenous RT may represent a new molecular target in the treatment of human renal clear-cell carcinoma, a neoplasm with very low sensitivity to standard pharmacological therapies. Efavirenz and nevirapine, 2 non-nucleosidic RT inhibitors commonly used in HIV patients, either induced a reversible downregulation of cell proliferation or enhanced cell differentiation in primary cultures of human renal carcinoma cells characterized by high levels of endogenous RT activity. Both agents upregulated the expression of the vitamin D receptor and calbindin 28k genes, which are constitutively expressed in renal tubular cells, and induced vitamin D signaling by enhancing the ability of tumor cells to upregulate the vitamin D-dependent gene, CYP24. Furthermore, efavirenz- and nevirapine-differentiated tumor cells exhibited an immunogenic phenotype with an increased expression of HLA-I and CD40 antigens and an enhanced ability to elicit a specific T-cell response in mixed lymphocyte/tumor-cell cultures. Indeed, renal carcinoma cells exposed to efavirenz induced a CD8(+)CCR7-CD45RA(-) effector memory T-cell phenotype, whereas untreated RCC cells induced a CD8(+)CCR7(+)CD45RA(-) central memory T-cell phenotype. These data suggest that RT inhibitors may be a novel tool in the treatment of human renal clear-cell carcinoma, potentially able to enhance the immunogenic potential of tumor cell.
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PMID:Reverse transcriptase inhibitors induce cell differentiation and enhance the immunogenic phenotype in human renal clear-cell carcinoma. 1835 78

Similar to mechanisms of recruitment of activated leukocytes to inflamed tissues, selectins mediate adhesion and extravasation of circulating cancer cells. Our objective was to determine whether sialyl Lewis X modified core 2 O-glycans (C2-O-sLe(X)) present on colon and hepatic carcinoma cells promote their adhesion and invasion. We examined membrane expression of C2-O-sLe(X), selectin binding, invasion of human colon and hepatic carcinoma cell lines, and mRNA levels of alpha-2,3 fucosyltransferase (FucT-III) and core 2 beta-1,6 N-acetylglucosaminyltransferase (C2GnT1) genes, necessary for C2-O-sLe(X) synthesis, by quantitative reverse-transcriptase (RT) PCR. Synthesis of core 2 branched O-glycans decorated by sLe(X) is dependent on C2GnT1 function and thus we determined enzyme activity of C2GnT1. The cell lines that expressed C2GnT1 and FucT-III mRNA by quantitative RT-PCR were highly positive for C2-O-sLe(X) by flow cytometry, and colon carcinoma cells possessed highly active C2GnT1 enzyme. Cells bound avidly to E-selection but not to P- and L-selectin. Gene knock-down of C2GnT1 in colon and hepatic carcinoma cells using short hairpin RNAs (shRNA) resulted in a 40-90% decrease in C2-O-sLe(X) and a 30-50% decrease in E-selectin binding compared to control cells. Invasion of hepatic and colon carcinoma cells containing C2GnT1 shRNA was significantly reduced compared to control cells in Matrigel assays and C2GnT1 activity was down-regulated in the latter cells. The sLe(X) epitope was predominantly distributed on core 2 O-glycans on colon and hepatic carcinoma cells. Our findings indicate that C2GnT1 gene expression and the resulting C2-O-sLe(X) carbohydrates produced mediate the adhesive and invasive behaviors of human carcinomas which may influence their metastatic potential.
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PMID:C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells. 2128 32

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