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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PDGF-B released from colon tumor cells regulated tumor growth in athymic mice in a paracrine manner by inducing blood vessel formation. A positive correlation was found between expression of PDGF B-chain in cells grown in vitro and the number of factor VIII-positive blood vessels in tumors induced by three classes of colon carcinoma cell lines. Elevated expression of PDGF-B was also correlated with tumor size. Each cell line had the same mutations in the colon cancer genes APC, DCC, and p53 and had wild type c-K-ras genes (Huang et al. [1994] Oncogene, 9:3701-3706.) eliminating the possibility that any differences in tumor blood vessel formation were due to mutations and/or deletions in these genes. Colon carcinoma cells released biologically active PDGF capable of stimulating the growth of NIH3T3 cells, which was inhibited by neutralizing antisera to PDGF-AB chains. An inverse correlation was found between induction of factor VIII-positive blood vessels and expression of vascular endothelial growth factor (VEGF), while no correlation was seen with expression of either TGF alpha or k-FGF. Basic fibroblast growth factor (FGF) expression was not detected in these tumor cells. TGF beta 1 was capable of inducing PDGF-B expression in the undifferentiated U9 colon carcinoma cell line, but this sensitivity was not seen in differentiated cells. In contrast, TGF beta 1 inhibited VEGF expression in both undifferentiated cells and differentiated colon cancer cells. Thus, TGF beta 1 has two roles in the growth of undifferentiated U9 colon carcinoma cells in vivo: direct stimulation of cell proliferation as we have showed in earlier studies, and an increase in angiogenesis by inducing PDGF-B.
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PMID:Platelet-derived growth factor-B increases colon cancer cell growth in vivo by a paracrine effect. 759 1

We studied the increasing expression of the p53 tumor suppressor gene in Sprague-Dawley rats, chemically induced to develop colon cancer. p53 expression was evaluated histochemically at various stages of tumor progression (during a period of 40 weeks) that can be followed by colonic hyperproliferation labeled by 3H-thymidine incorporation. We found that high level nuclear expression of p53 protein correlates with progression of malignancy in carcinogen-induced animals, whereas cytoplasmic staining is related to the onset and early development of malignancy.
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PMID:Histochemical studies of progressive p53 mutations during colonic carcinogenesis in Sprague-Dawley rats induced by N-methyl-N-nitro-nitrosoguanidine or azoxymethane. 759 92

We evaluated the histopathological and immunohistochemical findings of 41 superficial early colorectal carcinomas within 20 mm in diameter and twice of normal mucosa in height for the development. These colorectal cancers were divided into intramucosal carcinoma (21 lesions) and submucosal invasive carcinoma (20 lesions), and classified into two groups: superficial elevated type (25 lesions) and superficial depressed type (16 lesions). The average maximum diameter of superficial elevated type was larger than it of superficial depressed type, furthermore the increase in tumor diameter and the pattern of the overexpression of p53 protein was correlated to the invasivity. On the other hand, we found the submucosal invasion and the overexpression of p53 protein in the smaller depressed type carcinoma. Considering the circumstances mentioned above, we recognized the different development between superficial elevated type and superficial depressed type in the superficial early colon cancer, and thought superficial depressed type was more invasive.
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PMID:[Development and expression of p53 in superficial early colorectal carcinoma]. 760 14

The diet contains various mutagens and carcinogens that can be classified into three groups: naturally occurring chemicals, synthetic compounds and compounds produced by cooking. The first group includes mycotoxins and plant alkaloids while the second is exemplified by food additives and pesticides. The third includes polycyclic aromatic hydrocarbons and heterocyclic amines (HCAs). HCAs are mutagenic to microbes and eukaryotes and their precursors are creatine or creatinine, sugars, and amino acids in meat and fish. Among 10 HCAs so far examined for carcinogenicity in rodents, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced colon cancer in rats. PhIP is an especially interesting compound inducing colon tumors specifically in male F344 rats and only very rarely in females, which develop mammary carcinomas at high frequency instead. Since induced DNA adduct levels, determined by the 32P-postlabeling method, were found to be almost the same in male and female F344 rats adduct formation in itself is not directly responsible for carcinogenesis. We established, however, that PhIP causes increased cell proliferation in colon mucosa but not in the non-target liver or kidney of male rats. Induction of cell proliferation is therefore possibly an additional important factor determining carcinogenic organ specificity. In terms of molecular alteration ras family gene mutations are very rare and no mutations are evident in the p53 gene in colon tumors induced by HCAs. Their development due to HCAs can thus be considered an appropriate experimental model for human colon tumors in which ras or p53 gene activation is not involved. Since HCAs are genotoxic compounds, a causal role in some stage of human colon carcinogenesis is plausible. Exposure to HCAs should accordingly be avoided as far as possible.
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PMID:Carcinogenic factors in food with relevance to colon cancer development. 769 98

CpG dinucleotides are the target of about one third of transition mutations found in human genetic diseases and tumors. Methylation at these sites is thought to be the cause of these genetic changes through spontaneous deamination of 5-methylcytosine. In order to define the contribution of 5-methylcytosine to the spectrum of p53 mutations in human cancers, we have determined the complete DNA methylation pattern along exons 5-8 of the human p53 gene by ligation-mediated polymerase chain reaction genomic sequencing. The study was conducted with nine different types of normal human tissue and cell lines, including skin fibroblasts, keratinocytes, lung epithelial cells, mammary epithelial cells and colonic mucosa cells. We found that the p53 sequences along exons 5-8 are completely methylated at every CpG site, including 46 different sites on both DNA strands. This methylation pattern is tissue-independent suggesting that tissue-specific methylation does not contribute to the differential mutation patterns seen in tumors. The occurrence of mutational hotspots at specific CpG sites is not related to selective methylation of only a subset of CpGs but may rather depend on a selection bias for particular amino acid changes. Our results are not inconsistent with theories that mutations in tumors with high CpG mutation rates, like colon cancer, are caused by spontaneous deamination of 5-methylcytosine and mutations in tumors with a lack of CpG involvement reflect superimposed fingerprints from exogenous carcinogens. However, given the lack of tissue specificity of methylation, alternative explanations (eg targeting of methylated CpG sites by tissue-selective carcinogens) should be considered to explain the high percentage of CpG mutations in some tumor types.
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PMID:Complete and tissue-independent methylation of CpG sites in the p53 gene: implications for mutations in human cancers. 773 3

Tumor suppressor genes have been identified by the occurrence of mutations in many families with hereditary forms of cancer, exposed during development of the tumor by loss of heterozygosity. They have a number of diverse functions. For example, both the RB gene of retinoblastoma and the p53 gene, which is commonly mutated in breast and colon cancer among others, produce proteins involved in distinct steps of cell cycle control, while the nm23 product prevents metastasis. Here we review the data developed until now on the possible presence and role of mutations in these and other tumor suppressor genes in breast cancer. A more complete understanding of the tumor suppressor genes could not only provide diagnostic information, but could lead to specific gene therapy to replace suppressor functions lost in individual tumors.
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PMID:Tumor suppressor genes and their roles in breast cancer. 781 83

Transforming growth factor-beta (TGF-beta) inhibits cell cycle progression of many types of human cells by arresting them in the G1 phase of the cell cycle. The arrest is mediated through interactions of various cyclin-dependent protein kinases (CDKs) and their inhibitors. We demonstrate that treatment with TGF-beta induces increased levels of WAF1/Cip1/p21, a potent inhibitor of various cyclin-CDK kinase activities, in two colon cancer cell lines (LS1034 and LS513), which are sensitive to TGF-beta-induced growth arrest. The induction in at least one of these cell lines (LS1034,p53-) is p53-independent. No WAF1 induction was observed after TGF-beta treatment in a third cell line (HT-29), which is completely insensitive to the cytoinhibitory effect of TGF-beta. In both LS513 and LS1034, WAF1 induction correlated with reduced cyclin E-associated kinase activity in vitro and suppression of the retinoblastoma susceptibility gene (Rb) protein phosphorylation in vivo. In addition, WAF1 was physically associated with cyclin E in the two sensitive cell lines. These results suggest that WAF1/Cip1/p21 is a mediator of cellular sensitivity to TGF-beta.
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PMID:Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect. 789 Jun 1

Human colon cancer development is associated with the accumulation of mutations and deletions in the suppressor genes DCC, APC and p53 and mutations in the dominant oncogene K-ras, with loss of wild type alleles. In earlier studies we had observed that about half of the resected human colon cancers placed into primary culture were growth stimulated by TGF beta 1. This group included the more advanced cancers which were either poorly differentiated primary-site cancers or metastases. In contract, the more differentiated colon cancers were inhibited or unaffected by TGF beta 1, indicating that a switch in response to TGF beta 1 occurs during colon cancer progression. Different sublines of the HT29 colon carcinoma cell line model the resected cancers, responding to TGF beta 1 by proliferation, inhibition or no growth modulation. The current study shows that while the poorly differentiated, TGF beta 1-stimulated sublines are most tumorigenic, all the sublines have the same spectrum of mutations: truncating mutations in both APC (adenomatous polyposis coli) alleles, no activated ras genes, mutated and thus overexpressed p53, and very low expression of DCC compared to normal colon cells. Genes other than the four already implicated in colon carcinoma evolution are responsible for the mitogenic response to TGF beta 1 found in the more advanced cancers.
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PMID:The capacity for growth stimulation by TGF beta 1 seen only in advanced colon cancers cannot be ascribed to mutations in APC, DCC, p53 or ras. 797 Jul 29

Reports of cases of flat-type colorectal tumors are increasing in Japan, but almost nothing has been elucidated about the genetic abnormalities of these tumors. In this study, we have examined p53 mutations in six cases of colon cancer cell lines, 22 cases of flat-type colorectal tumors, and 27 cases of polypoid-type colorectal tumors using the polymerase chain reaction (PCR) and temperature-gradient gel electrophoresis (TGGE); the latter has recently been developed as a screening method for gene mutations. p53 mutations were observed in four colon cancer cell lines, six flat-type colorectal tumors, and three polypoid-type colorectal tumors, all of which were analyzed by direct sequencing. These mutations were observed only in adenomas with high-grade dysplasia and in colorectal cancers but not in adenomas with low-grade dysplasia. These observations suggest that p53 gene mutations are involved in flat-type as well as polypoid-type colorectal tumors at relatively later stages of carcinogenesis and that TGGE seems to be useful as one of the rapid screening methods.
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PMID:p53 mutations in flat- and polypoid-type colorectal tumors detected by temperature-gradient gel electrophoresis. 808 16

Genetic alterations of several oncogenes and tumor suppressor genes are associated with human colorectal carcinogenesis. Especially in mutations, the K-ras, p53, APC and DCC gene frequently occurred, and these gene alterations seem to have important roles in colorectal carcinogenesis. We investigated 28 human colon cancer specimens obtained from surgery and five human colon cancer cell lines by PCR-SSCP assay, PCR-OSH assay, RT-PCR or sequencing method. Forty percent of cancers from surgical specimens had Ki-ras 2 (codon 12/13), p53 (Exon 5-8), APC (MCR) gene mutations, and fifty-seven percent of them had lower expression of DCC gene that of normal matched colon mucosa of the same patient. G to A transition was the most frequent in K-ras mutational spectrum in this case; 25% of patients had both k-ras and p53 gene point mutations. Form the results, we concluded that it in colorectal carcinogenesis for both K-ras and p53 gene point mutations might not necessary occur.
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PMID:[Genetic alterations of human colorectal cancer]. 810 90


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