Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitogenic role of estradiol on the growth of colon cancer was examined in mice. Sham-operated or ovariectomized mice were injected with cancer cells and received estradiol treatment. Tumor growth was noted: tumor weights were higher in female than male mice. The growth of the tumors was least in ovariectomized mice and highest in estradiol-treated ovariectomized mice. Tumor messenger RNA (mRNA) levels for ornithine decarboxylase (ODC) and proto-oncogenes c-myc, c-fos, and H-ras were examined. Two transcripts (2.2 and 2.7 kilobase pairs) of ODC were observed. The steady-state mRNA levels for ODC paralleled the changes observed in the weight of the tumors in all groups of animals. Less dramatic changes were observed in c-myc mRNA levels. No significant differences were observed in the mRNA levels for H-ras and c-fos. It thus appears likely that an increase in the ODC mRNA levels and, to a lesser extent, an increase in c-myc mRNA levels may be some of the important mechanisms by which estradiol mediates its growth effects on colon cancer cells in vivo.
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PMID:Estradiol is trophic for colon cancer in mice: effect on ornithine decarboxylase and c-myc messenger RNA. 145 76

Aberrant crypt foci represent the earliest detectable lesions of colon cancer. The expression of c-fos in these aberrant crypts was determined by in situ hybridization and immunohistochemistry. These lesions were induced in the colonic epithelium with azoxymethane using the rat model system. Expression of c-fos was markedly increased in the aberrant colonic crypts. Increases of approximately 60 and approximately 70% in the proportion of epithelial cells labelled were observed in the early and advanced aberrant crypts respectively. This was found to be statistically significant (P less than 0.001). Consistent with cell proliferation patterns in the colonic crypts, the epithelial cells of the lower crypt had greater levels of c-fos mRNA than those of the upper part of the crypts. In addition, immunohistochemical staining with c-fos polyclonal antibodies demonstrated increased levels of c-fos protein in aberrant crypts. This combined approach using in situ hybridization and immunohistochemistry has shown that increased c-fos expression at the RNA level in these lesions is associated with increased amounts of c-fos protein. Since c-fos has been implicated in the process of cell proliferation and differentiation, modifications in its expression may be significant to understanding the mechanisms whereby preneoplastic lesions transform to neoplastic lesions in colon cancer.
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PMID:Colonic aberrant crypt foci are associated with increased expression of c-fos: the possible role of modified c-fos expression in preneoplastic lesions in colon cancer. 157 9

The biosynthesis of the polyamines, putrescine, spermidine and spermine, is temporally linked with expression of many growth related genes. Our previous studies have shown that generalized polyamine depletion of the human colon cancer cell line COLO 320 by 2-difluoromethylornithine is associated with decreased transcription of the c-myc, c-fos, and ornithine decarboxylase (ODC) genes. In the current study, the role of individual polyamines was further defined by the use of a specific inhibitor of spermidine synthase, S-adenosyl-1,8, diamino-3-thio-octane (AdoDATO), and a spermine analogue, N1,N12 bis(ethyl)spermine. Our data demonstrate that depletion of spermidine results in a 60-90% decrease in c-myc mRNA steady state levels. In contrast, c-fos mRNA levels are decreased only when both spermidine and spermine are diminished. Furthermore, ODC mRNA levels are increased when all polyamines are decreased by DFMO, but are unaffected by a selective reduction in intracellular spermidine levels by AdoDATO. These studies suggest that individual polyamines may have a selective role in the expression of specific growth related genes.
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PMID:Modulation of growth gene expression by selective alteration of polyamines in human colon carcinoma cells. 251 47

Six colon cancer cell lines, 13 colon tumors and ten normal colon tissues were analyzed for RNA expression using probes for c-myc, c-k-ras, c-myb, and c-fos and for the p53, TGF-alpha, and EGF receptor genes. No aberrant transcripts were detected. Levels of expression in tumors ranged from two-fold below that of normal tissue when the v-fos probe was used to 10 fold above the normal level when the c-myc probe was used. Enhanced c-myc expression was also observed in the cell lines. Southern and DNA dot blot analyses revealed c-myc amplification in three of the six cell lines.
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PMID:Oncogene expression in adenocarcinomas of the colon and in colon tumor-derived cell lines. 328 75

One of the extension proteins on the carboxy terminus of ubiquitin was reported as the ribosomal protein S27a. We have cloned a gene which encodes this ubiquitin hybrid protein from a complementary DNA library of a human colon carcinoma cell line. Northern blot analysis of surgical specimens from colon cancer patients showed that these messenger RNA levels were higher in tumor tissue than in adjacent normal mucosa. Furthermore, to investigate the role of this novel ubiquitin hybrid gene in cellular growth control, the responsiveness of this gene to serum growth factors was examined. Within 30 min after serum or 12-O-tetradecanoylphorbol-13-acetate stimulation, its messenger RNA expression in rat fibroblast cells (Rat 1) was increased. Nuclear runoff transcription studies showed that the kinetics of induction of this gene is almost identical to that of protooncogene c-jun or c-fos, the known early growth response genes. Thus, this ubiquitin hybrid gene appears to be a novel early growth response gene overexpressed in human colon cancer and warrants further studies in the pathogenesis of colorectal carcinoma.
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PMID:Ubiquitin-ribosomal protein S27a gene overexpressed in human colorectal carcinoma is an early growth response gene. 838 74

The main objectives were to determine the modulating effects of all-trans retinoic acid on the number, size and multiplicity of aberrant crypt foci as well as the in vivo expression of the genes c-myc and c-fos. These foci, which are hypothesized to be the pre-malignant lesions of colon cancer, were induced in Sprague-Dawley rats with a single injection of azoxymethane. Rats were fed either a control diet (AIN-76) or the control diet to which had been added 75 mg/kg or 150 mg/kg all-trans retinoic acid. Within 4 weeks, we observed that the diets containing all-trans retinoic acid reduced the total number and multiplicity of aberrant crypt foci in the colon. However, all-trans retinoic acid increased the size of the lesions that persisted, possibly due to a greater proportion of lesions with dilated crypts. In situ hybridization and immunohistochemistry were performed on the colons for the in vivo analysis of gene expression in these lesions. The expression of myc-specific mRNA and protein in aberrant crypt foci significantly decreased with both levels of all-trans retinoic acid. In contrast, fos-specific mRNA and protein in aberrant crypt foci significantly increased when 150 mg/kg all-trans retinoic acid was added to the diet. The most important findings of this investigation are that intervention with all-trans retinoic acid in the pre-malignant stage of colon carcinogenesis is effective in decreasing the number and growth of aberrant crypt foci and altering the expression of the c-myc and c-fos genes.
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PMID:Effects of all-trans retinoic acid as a potential chemopreventive agent on the formation of azoxymethane-induced aberrant crypt foci: differential expression of c-myc and c-fos MRNA and protein. 844 5

Protooncogenes are cell cycle-related genes that are involved in cell growth of proliferation. Alterations in the level of expression of these genes, or expression of aberrant gene productions, have been observed in tumors and precancerous conditions. To determine if expression of these genes is altered in patients with inflammatory bowel disease (IBD) --who are at risk for development of colon cancer--we assayed transcripts of 15 protooncogenes in colonic epithelial cells of IBD patients and controls. Nine of these genes (H-ras, c-myc, c-fos, c-jun, junB, N-myc, c-abl, c-yes, and p53) were expressed in epithelial cells, whereas two (RB1 and N-ras) were not. expression of four other genes (c-src, K-ras, c-raf, and c-myb) was observed, but the intensity of these bands was too low for densitometric analysis. The steady-state levels of transcripts of H-ras and five nuclear protooncogenes (c-myc, c-fos, c-jun, junB, and N-myc) were lower in epithelial cells from involved or uninvolved IBD samples than in normal epithelial cells from either sporadic colon cancer or diverticulitis patients. The level of c-fos mRNA was two- to threefold higher in involved than in uninvolved areas of the colons of two ulcerative colitis (UC) patients, but not in one Crohn's disease (CD) patient. Message abundance of c-abl transcripts was two- to threefold lower in UC epithelial cells than in either the CD or control samples. The steady-state level of c-yes-encoded mRNA was considerably higher in IBD patients resected for colon cancer than in patients resected for active chronic IBD or in controls. The level of p53 message was constant in these samples. Increased levels of c-fos mRNA in involved UC relative to uninvolved UC may be related to the disease process. Decreased expression of c-abl transcript in UC may be a diagnostic marker for UC and may be related to the rate of cell turnover in these diseases. Enhanced expression of c-yes in IBD patients with tumors compared to active chronic IBD and controls suggests that expression of this gene may be a marker for development of colon cancer in IBD.
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PMID:Expression of protooncogene-encoded mRNA by colonic epithelial cells in inflammatory bowel disease. 867 85

This study determines the prognostic role of c-fos protein expression in patients with colon cancer who previously failed therapy with 5-fluorouracil (5-FU). Patients with advanced colorectal who were refractory to 5-FU therapy received irinotecan (CPT-11) by a 90-minute intravenous infusion at a dose of 125 mg/m2 weekly for four weeks followed by a 2-week rest period were eligible for oncogene assessment. C-fos protein expression was evaluated using archival formalin-fixed, paraffin-embedded tumor tissue, and an automated immunoperoxidase histochemical technique. Thirty-five patients were found to have > 25% positive c-fos activity. Nine patients had no detectable c-fos expression. Characteristics of patient subgroups were not different, however, the median survival of patients with elevated c-fos expression from the time of treatment with CPT-11 was 436 days, whereas patients with no detectable c-fos expression had a median survival of 365 days (p = 0.045). C-fos exhibits a casual role in the initiation of apoptosis and is implicated in differentiation and proliferation. It has been shown to correlate with poor survival in breast cancer, but improved survival in patients with astrocytic glioma. In this analysis, there is a suggestion that elevated c-fos expression is a good prognostic marker for patients with refractory colorectal carcinoma.
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PMID:Improved survival in patients with advanced colorectal carcinoma failing 5-fluorouracil who received irinotecan hydrochloride and have high intratumor C-fos expression. 978 1

An 8.5-kb 5'-flanking region of the human urokinase-type plasminogen activator receptor (uPAR) gene was cloned and the detailed uPAR promoter region defined in an 188-bp fragment between bases -141 and +47 relative to the transcription-start site. 5'-Deletion to -100 and -60 in the region abolished its promoter activity, indicating that an 81-bp segment between -141 and -61, which contains a proximal AP-1 site at position -70, is required for uPAR promoter activity. Nuclear extracts from HCT116 cells contain proteins that specifically bind to the AP-1 site. Mutation of the AP-1 motif reduced uPAR promoter activity in comparison with the wild-types. Induction of uPAR expression by phorbol ester requires this AP-1 motif in colon cancer cells. Cotransfection with the c-jun and c-fos expression vectors stimulated the uPAR promoter activity four- to fivefold. These results demonstrate that the proximal AP-1 motif is responsible for approximately 50% of the basal expression of the uPAR gene.
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PMID:A region between -141 and -61 bp containing a proximal AP-1 is essential for constitutive expression of urokinase-type plasminogen activator receptor. 1044 77

Theaflavin (TF-1), theaflavin-3-monogallate and theaflavin-3'-monogallate mixture (TF-2), and theaflavin-3,3'-digallate (TF-3) are the major black tea polyphenols. Here we compared the effects of these polyphenols on cell growth, apoptosis, and gene expression in normal and cancerous cells. We showed that TF-2 (10-50 microM) inhibited the growth of SV40 transformed WI38 human cells (WI38VA) and Caco-2 colon cancer cells but had little effect on the growth of their normal counterparts. The IC50s of TF-2 for the growth inhibition of WI38 and WI38VA cells were, respectively, 300 and 3 microM. The other two black tea polyphenols, TF-1 and TF-3, did not exhibit such differential growth-inhibitory effect. TF-2, but not TF-1 or TF-3, induced apoptosis in transformed WI38VA cells but not in normal WI38 cells, suggesting that apoptosis was responsible, at least in part, for the differential growth-inhibitory effect of TF-2. Cox-2 has been implicated in intestinal carcinogenesis. Among the tea polyphenols tested, TF-2 and, to a lesser degree, (-)-epigallocatechin gallate inhibited cyclooxygenase (Cox)-2 gene expression. TF-2 at 50 microM completely blocked the serum-induced Cox-2 gene expression at both mRNA and protein level. Other genes, including c-fos, c-myc, thymidine kinase, proliferating cell nuclear antigen, BRCA1, BRCA2, and Cox-1, were not significantly affected by TF-2. These findings suggest that TF-2 may be responsible, at least in part, for the chemopreventive activity in black tea extracts.
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PMID:Differential effects of theaflavin monogallates on cell growth, apoptosis, and Cox-2 gene expression in cancerous versus normal cells. 1110 14


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