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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Signal transducer and activator of transcription 3 (STAT3) has oncogenic potential. The biological effects of STAT3 have not been studied extensively in the pathogenesis of colon cancer, nor has the role of Janus kinase 3 (JAK3), the physiological activator of STAT3, been evaluated. Here, we demonstrate that activated STAT3 (pSTAT3) and activated JAK3 (pJAK3) are expressed constitutively in two colon cancer cell lines, SW480 and HT29. To evaluate the significance of JAK3/STAT3 signaling, we inhibited JAK3 with AG490 and STAT3 with a dominant-negative construct. Inhibition of JAK3 down-regulated pSTAT3. The blockade of JAK3/STAT3 signaling significantly decreased viability of colon cancer cells due to apoptosis and cell-cycle arrest through down-regulation of Bcl-2, Bcl-X(L), Mcl-1, and cyclin D2 and up-regulation of p21(waf1/cip1) and p27(kip1). We also examined histological sections from 22 tumors from patients with stage II or stage IV colon cancer and found STAT3, JAK3, and their activated forms to be frequently expressed. Furthermore, quantitative reverse transcriptase-polymerase chain reaction identified JAK3 mRNA in colon cancer cell lines and primary tumors. Our findings illustrate the biological importance of JAK3/STAT3 activation in the oncogenesis of colon cancer and provide novel evidence that JAK3 is expressed and contributes to STAT3 activation in this malignant neoplasm.
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PMID:Constitutive activation of JAK3/STAT3 in colon carcinoma tumors and cell lines: inhibition of JAK3/STAT3 signaling induces apoptosis and cell cycle arrest of colon carcinoma cells. 1619 33

Caffeic acid phenethyl ester, an active component of propolis, has been implicated in the regulation of cell growth and apoptosis, although the exact mechanism of this activity has not been elucidated. In this study, we explored the effects of caffeic acid phenethyl ester on growth, cell cycle, apoptosis and beta-catenin/T-cell factor signaling in human colon cancer cells. Using two human sporadic colon cancer cell lines (HCT116 and SW480), we assayed for cell growth inhibition, cell cycle and apoptosis induction. We also assayed for beta-catenin and downstream target genes (cyclin D1 and c-myc) mRNA and protein expression by reverse transcriptase-polymerase chain reaction and Western blot analysis. Beta-catenin localization was detected by indirect immunofluorescence. Beta-catenin/T-cell factor transcriptional activity was determined by transient transfection and reporter gene assay. Caffeic acid phenethyl ester completely inhibited growth, and induced G1 phase arrest and apoptosis in a dose-dependent manner in both HCT116 and SW480 cells. Treatment of human colon cancer cells with apoptotic concentrations of caffeic acid phenethyl ester resulted in a dose-dependent and time-dependent loss of total beta-Catenin protein, associated with decreased nuclear beta-catenin. Caffeic acid phenethyl ester reduced the expression of cyclin D1 and c-myc in a dose-dependent and time-dependent manner. We proved that caffeic acid phenethyl ester markedly suppressed the transcriptional activity of beta-catenin/T-cell factor in both HCT116 and SW480 cells depending on the concentration of caffeic acid phenethyl ester. These results indicate that caffeic acid phenethyl ester is an excellent inhibitor of beta-catenin/T-cell factor signaling in colon cancer cell lines and suggest that caffeic acid phenethyl ester merits further study as an agent against colorectal cancers.
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PMID:Caffeic acid phenethyl ester induces growth arrest and apoptosis of colon cancer cells via the beta-catenin/T-cell factor signaling. 1692 25

Produced by dietary fiber, butyrate is a potential chemopreventive agent against colon cancer. It stimulates proliferation of normal colonic epithelial cells but induces growth inhibition, differentiation, apoptosis, or a combination of effects in colon carcinoma cells. In this study, we used cDNA membrane arrays and real-time reverse transcriptase-polymerase chain reaction to identify stress genes that were differentially regulated by sodium butyrate (NaB) in HT 29 human colon carcinoma cells. The results indicated that a group of heat shock protein (hsp) genes were upregulated by 3 mM NaB within the first 24 hours of exposure. Because the transcription of hsp genes is under the control of heat shock factors (HSFs), we measured the effects of overexpressed HSF-1 on the responses of HT 29 cells to NaB. Overexpression of HSF-1 inhibited NaB-induced differentiation as measured by alkaline phosphatase activity and carcinoembryonic antigen expression. These results suggest that increased expression of HSFs and Hsps might render colon carcinoma cells resistant to the chemopreventive effects of butyrate.
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PMID:Overexpression of heat shock factor 1 inhibits butyrate-induced differentiation in colon cancer cells. 1700 92

Overexpression of aspartyl (asparaginyl) beta-hydroxylase (AAH) has been demonstrated in hepatocellular carcinoma, cholangiocarcinoma, and pancreatic carcinoma. AAH has an important role in regulating cell motility and invasiveness. Humbug is a truncated homolog of AAH, with a role in calcium regulation. The present study examines the prognostic use of AAH and humbug gene expression in stage II colon cancer. One hundred thirty cases of TNM stage II colon carcinoma were retrieved from the Rhode Island Hospital pathology archives. Tissue microarrays were immunostained with the FB50 and 15C7 monoclonal antibodies generated to recombinant AAH. However, FB50 also recognizes humbug. In addition, AAH and humbug expression was analyzed in samples of colon cancer and adjacent normal mucosa by real-time quantitative reverse transcriptase-polymerase chain reaction. Humbug (FB50) expression was localized to the tumor cytoplasm, whereas normal colonic epithelium did not exhibit significant immunoreactivity. Humbug staining was detected in 85% of the neoplasms, 23% of which stained strongly. Strong humbug immunoreactivity positively correlated with nuclear grade (P = .006) and inversely with survival (P = .027). In contrast to humbug, AAH (15C7) immunoreactivity was seen in normal and neoplastic epithelium. There was no correlation between AAH immunoreactivity and tumor grade, or survival. Correspondingly, reverse transcriptase-polymerase chain reaction studies demonstrated up-regulation of humbug but not AAH in 95% of colon carcinomas relative to adjacent colon cancer-free mucosa (P < .0001). This study demonstrates that high levels of humbug immunoreactivity in colon carcinomas correlate with histologic grade and tumor behavior, suggesting that humbug can serve as a prognostic biomarker of TNM stage II colon cancers. In addition, molecular studies demonstrated that the increased levels of FB50 detected were due to humbug, as opposed to AAH overexpression.
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PMID:Prognostic value of humbug gene overexpression in stage II colon cancer. 1702 Jul 79

1,2:5,6-Di-O-isopropylidene-alpha-d-glucofuranose on mild oxidation, reduction, fluorination, and deisopropylidenation followed by acetylation gave peracetylated 3-deoxy-3-fluoro-d-glucopyranose. This was coupled with silylated N(4)-benzoyl cytosine. The nucleoside was deacetylated and after several subsequent protection and deprotection steps afforded the desired 3-fluoro-2-keto-beta-d-glucopyranosyl derivatives. These novel synthesized compounds were evaluated for antiviral and cytotoxic activities against rotavirus, vesicular stomatitis virus, and the human colon adenocarcinoma cell line Caco-2, and have a promising potential in combating the rotaviral infections and in the treatment of colon cancer. As compared to AZT, a nucleoside analogue of reverse transcriptase inhibitor, the novel synthesized 1-(3,4-dideoxy-3-fluoro-beta-d-glycero-hex-3-enopyranosyl-2-ulose)-N(4)-benzoyl cytosine showed to be more effective at lower concentrations in inhibition of rotavirus infection as well as in the same range of antitumor activity.
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PMID:Fluoro-ketopyranosyl nucleosides: synthesis and biological evaluation of 3-fluoro-2-keto-beta-D-glucopyranosyl derivatives of N4-benzoyl cytosine. 1707 49

Since the efficacy of chemotherapy can be enhanced by targeting to specific receptors on tumors, we investigated the expression of LH-RH receptors in 5 human colon cancer lines and the effects of cytotoxic LH-RH analogs on these tumors. Nude mice bearing HT-29, HCT-116, HCT-15, LoVo and Colo-320DM cancers were treated with cytotoxic LH-RH analogs AN-152 and AN-207 or their respective cytotoxic radicals doxorubicin (DOX) and 2-pyrrolino-DOX (AN-201). The reduction in tumor growth was evaluated, and cell proliferation characteristics as well as apoptosis were analyzed by histological methods. LH-RH receptors on the tumors were investigated by radioligand binding assays and their mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). All 5 colorectal cancer lines expressed high affinity binding sites for LH-RH, and mRNA for the LH-RH receptors. Both cytotoxic LH-RH analogs AN-152 and AN-207 powerfully inhibited growth of all colon cancers. AN-207 had the strongest effect on HT-29 and HCT-116 tumors, and AN-152 was the most effective on Colo-320DM cancers. Cytotoxic radicals AN-201 and DOX were less effective on these 3 tumors, but had effects similar to AN-152 and AN-207 on HCT-15 and LoVo carcinomas. The four cytotoxic compounds also differently affected apoptosis and proliferation rate of the various tumor lines. Our findings suggest that cytotoxic LH-RH analogs should be considered for the therapy of patients with advanced colorectal carcinoma.
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PMID:LH-RH receptors in human colorectal cancers: unexpected molecular targets for experimental therapy. 1748 70

It has been reported, as a result of Western blot analyses, that FKBP51 is expressed in various tissues, but that it is not expressed in the pancreas, lung, colon, stomach, or spleen. In this paper, we show, using Western blot analyses, reverse transcriptase polymerase chain reaction, and immunohistochemical analyses of samples from colon cancer patients, that both normal epithelial cells and adenocarcinoma in the human colon express FKBP51, and that there are no significant differences in the expressions of FKBP51 between them. We also show that FKBP51 suppresses the proliferation of colorectal adenocarcinoma, possibly due to the suppression of functions of the glucocorticoid receptors.
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PMID:FKBP51 expressed by both normal epithelial cells and adenocarcinoma of colon suppresses proliferation of colorectal adenocarcinoma. 1844 59

CD40, a member of the tumor necrosis factor receptor superfamily, is widely expressed on various cell types. Some studies show that CD40 expression is related to several carcinomas, where its function remains largely unknown. This study investigated the expression of CD40 on colon cancer, and evaluated the effect of recombinant soluble human CD40L (rshCD40L) on colon cell lines. CD40 expression on the primary colon cancer samples was detected by immunohistochemistry. The expression of CD40 on colon cell lines was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry. To examine the effects of rshCD40L, the growth-inhibitory activity of rshCD40L on colon cancer cell was examined by MTT assay and the proportion of apoptotic tumor cells was examined in the TUNEL assay. Results showed that CD40 is expressed in human colon primary tumor. Expression of CD40 was elevated in 3 out of 4 colon cell lines examined by RT-PCR and flow cytometry. CD40 expression could be induced by interferon-gamma (IFN-gamma). CD40 ligand, rshCD40L, significantly inhibited the proliferation of the CD40(+) colon cancer cell lines. The inhibition could also be enhanced by IFN-gamma in HCT116 and SW48 cell lines. In addition, rshCD40L induced apoptosis of the CD40(+) colon cancer cell lines. Theses results suggest that CD40 present in colon cancer, and rshCD40L may be of clinical use to inhibit human colon cancer growth.
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PMID:Expression of CD40 and growth-inhibitory activity of CD40 ligand in colon cancer ex vivo. 1860 31

Recent studies demonstrated an epigenetic inactivation of the runt-related transcription factor 3 (RUNX3) gene in human colon cancer. However, it remains unclear whether RUNX3 is tumor suppressive in colon cancer and, if so, the underlying molecular mechanisms of this activity are still unknown. In the present study, we sought to determine the level of RUNX3 expression in human colon tumor specimens and used an animal model of colon cancer to determine the impact of RUNX3 expression on tumor growth and metastasis. First, we analyzed RUNX3 expression in 83 human colon tumor specimens using immunohistochemical, reverse transcriptase-polymerase chain reaction, and Western blot analysis. RUNX3 mRNA and protein expression levels were consistently lower in tumor tissue specimens than in matched normal colon tissue specimens. Also, restoration of RUNX3 expression in colon cancer cells using gene transfer inhibited colon tumor growth and metastasis in our animal model, which was consistent with inhibition of colon tumor growth in vitro. Collectively, our clinical and experimental data support the notion that RUNX3 is a tumor suppressor in human colon cancer.
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PMID:Inhibition of the growth and metastasis of human colon cancer by restoration of RUNX3 expression in cancer cells. 1894 60

A protein exhibiting an N-terminal amino acid sequence with some similarity to imidazoleglycerol phosphate synthase was purified from fresh Capparis spinosa melon seeds. The purification protocol entailed anion exchange chromatography on DEAE-cellulose, cation exchange chromatography on SP-Sepharose, and finally gel filtration by fast protein liquid chromatography on Superdex 75. The protein was adsorbed using 20 mM Tris-HCl buffer (pH 7.4) and desorbed using 1 M NaCl in the starting buffer from the DEAE-cellulose column and SP-Sepharose column. The protein demonstrated a molecular mass of 38 kDa in gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that it was monomeric. The protein inhibited proliferation of hepatoma HepG2 cells, colon cancer HT29 cells and breast cancer MCF-7 cells with an IC(50) of about 1, 40 and 60 microM, respectively. It inhibited HIV-1 reverse transcriptase with IC(50) of 0.23 microM. It inhibited mycelial growth in the fungus, Valsa mali. It did not exhibit hemagglutinating, ribonuclease, mitogenic or protease inhibitory activities.
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PMID:A protein with antiproliferative, antifungal and HIV-1 reverse transcriptase inhibitory activities from caper (Capparis spinosa) seeds. 1901 43


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