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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal cancer (CRC) has a strong familial component. Candidate genes for colorectal cancer have been identified through mutations in four mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) and genes that are deleted or mutated in tumors (DCC, APC, and p53). Linkage analysis of candidate loci/regions was performed in 10 kindreds ascertained for common colorectal cancer from the Utah Population Database. Evidence for linkage to candidate genes was assessed using two- or three-point logarithm of the odds ratio scores with markers spanning the region of localization. One kindred is linked to hMSH2 and also fits the criteria for hereditary nonpolyposis colorectal cancer, having early age of onset and high penetrance for CRC. The remaining nine kindreds are unlinked to the candidate genes tested. These kindreds have a later age of onset and a lower penetrance than hereditary nonpolyposis colorectal cancer kindreds. these results indicate that further unmapped susceptibility loci may be responsible for much of the familial aggregation of CRC.
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PMID:Genetic heterogeneity and unmapped genes for colorectal cancer. 864 Aug 29

Progress in development of a genetic model for colorectal tumorigenesis and human chemoprevention research may allow the mechanism-based identification of targets and chemopreventive agents that will protect against colorectal cancer. For example, numerous mutagenic events can occur throughout colorectal carcinogenesis, including loss of heterozygosity in tumor suppressor genes such as APC, MCC, DCC, and p53, as well as in oncogenes such as K-ras. Chemopreventive agents that inhibit mutagenic activity such as N-acetyl-l-cysteine, oltipraz, and nonsteroidal anti-inflammatory drugs may protect against these mutations. Also, agents such as perillyl alcohol and lovastatin that interfere with protein isoprenylation and, hence, inhibit oncogene activation may protect against aberrant K-ras expression. Hyperproliferation in normal mucosa, leading to growth and progression of neoplasia, are also aspects of colorectal carcinogenesis that can be controlled by chemopreventive agents. Calcium is a chemopreventive agent for which there is both clinical and experimental evidence of inhibition of cell proliferation in colon mucosa. Other examples of antiproliferative agents with potential chemopreventive efficacy in colon are 2-difluoromethylornithine, dehydroepiandrosterone, and selenium. Differentiating agents such as retinoids and deltanoids also may slow proliferation and progression. Antioxidants have potential for interfering with both mutagenicity and proliferation (e.g., by preventing oxidative activation of carcinogens and scavenging activated oxygen species generated during inflammation). The same mechanistic principles apply to identification of dietary chemopreventive intervention for colorectal carcinogenesis. For example, lowering dietary fat and increasing dietary fiber lead to lower colorectal mucosal proliferation, and cruciferous vegetables contain agents such as indoles and dithiolthiones that have shown antimutagenic activity.
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PMID:Genetic and cellular changes in colorectal cancer: proposed targets of chemopreventive agents. 867 84

It has been reported that several genes may be good indicators for determining biological behavior, including the prognosis, of colorectal cancers. We have summarized these reported genes, such as tumor suppressor gene, oncogenes, metastasis suppressor gene, adhesion molecules, growth factors, proteinases, and others, including microsatellite instability. Some of the genes such as p53, DCC, c-met, or matrix metalloproteinase are considered to be reliable for determining biological aggressiveness. We introduced several interesting genes which we are focusing using cDNA subtraction library analysis. We hope that these genes are well combined for best analysis of the biological behavior of colorectal cancers and use for practical clinical analysis. In addition, we hope that novel important genes indicative for prognosis will be found.
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PMID:[Prognostic factors of colon cancer from a molecular biology standpoint]. 868 33

In order to clarify the association between bcl-2 protein (Bcl-2) expression and genetic alteration, we investigated p53 and DCC (deleted in the colon carcinoma gene locus) gene abnormalities in Bcl-2-positive and -negative gastric carcinomas using a polymerase chain reaction/loss of heterozygosity (LOH) assay. Bcl-2 immunoreactivity was found in 25 of 178 (14%) gastric carcinoma cases. With these 25 positive cases, the proportion 18/87 (20.6%) of the total in early stages demonstrating invasion of the mucosa and/or submucosa was significantly greater (P = 0.013) than the 7/91 (7.7%) found for advanced tumors exhibiting invasion into or through the muscularis propria. However, there was no statistically significant variation between the proportions for differentiated (17/98 cases, 17.3%) and undifferentiated (8/80 cases, 10%) lesions. Sixteen Bcl-2-positive cases (9 cases were not studied because of insufficient specimen material to allow extraction of DNA) and 31 cases randomly selected from a Bcl-2-negative group were analyzed for the presence of p53-LOH or DCC-LOH and for p53 by immuno-histochemistry. The minority of the Bcl-2-positive group had p53-LOH and were immunopositive for p53 (P = 0.033, P = 0.028 respectively), while no association was found in the Bcl-2-negative category. In contrast, there was no correlation at all between Bcl-2 expression and DCC-LOH although the number of informative cases analyzed was too small to allow definite conclusions. These results indicate that Bcl-2 may be predominantly expressed at an early stage in gastric carcinomas, possibly in negative association with p53 gene abnormalities.
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PMID:Bcl-2 expression and allelic loss of the p53 gene in gastric carcinomas. 869 Jul 54

We have examined 41 cases of follicle centre cell lymphoma with fluorescent PCR of microsatellite repeats closely linked to or within six tumour suppressor gene loci (APC, DCC, P53, RB1, WT1 and NM23). These probes are highly informative with heterozygousity rates in the range of 57%-90%. In addition we have used four loci from chromosome 6 (D6S260, TNFa, D6S281 and D6S262) as control loci which are unlikely to be involved in the pathogenesis of lymphoma. Of 369 informative PCR reactions allele imbalance was identified in 38 (10%) and this was seen in 23 of the 41 cases. Looking at individual loci allele imbalance was seen in APC(1) 11%, APC(2) 12%, P53(1) 5%, P53 (2) 7%, WT1 5%, RB1 13%, DCC 18% and NM23 0%. This frequency of change was no different from that seen at the control loci D6S260 16%, TNFa 20%, D6S281 4% and D6S262 9%. In the indolent phase of germinal centre cell lymphoma there is therefore quite a high rate of allele imbalance at all loci but this is no higher in those loci linked to tumour suppressor genes.
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PMID:Allele imbalance at tumour suppressor loci during the indolent phase of follicle centre cell lymphoma. 872 37

This study concerns DNA ploidy, numerical changes of chromosomes 7, 8, 10, 17 and 18, and allelic losses at chromosomes 17p13.3 (flanking the p53 gene) and 18q21 (location of the DCC gene) in 31 freshly resected colorectal tumours. Cytological smears were used to determine DNA ploidy by image analysis, and chromosome numbers by fluorescence in situ hybridization (FISH) using chromosome-specific pericentromeric alpha-satellite DNA probes. Allelic losses were assessed by Southern blotting and by the polymerase chain reaction loss of heterozygosity method. Approximately 50% of the tumours were aneuploid. There was heterogeneity with respect to chromosome numbers, but gains and losses of chromosomes, or both, were detected in all carcinomas examined, including 10 that were nonaneuploid by image analysis. Trisomy 7 was found in 74% of the tumours, and monosomy of chromosome 18 in 32%. Allelic loss at chromosome 17p13.3 was evident in 13 of 26 informative cases, and only one case exhibited monosomy 17. In comparison monosomy 18 was found in 10 cases; 7 of them corresponded to approximately half of the cases with allelic loss within the DCC gene, and the other three were noninformative. These findings indicate that the loss of one chromosome 18 is an important mechanism producing allelic deletion of the DCC gene in colorectal carcinomas. Our data also suggest that monosomy 18 is a useful indicator for studying colorectal cancer progression on a cell by cell basis.
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PMID:Numerical chromosome alterations in colorectal carcinomas detected by fluorescence in situ hybridization. Relationship to 17p and 18q allelic losses. 876 33

Molecular alterations play a key role in the pathogenesis of gastrointestinal cancers. In the present paper we describe relevant molecular alterations in human pancreatic adenocarcinomas. Overexpression of growth factor receptors (EGF receptor, c-erbB2, c-erbB3, TGF beta receptor I-III), growth factors (EGF, TGF alpha, TGF beta-1-3, aFGF, bFGF), adhesion molecules (ICAM-1, ELAM-1) and gene mutations (p53, K-ras, DCC, APC) are present in a significant number of these tumors. These changes stimulate tumor growth and enhance the metastatic behavior of pancreatic cancer cells and thereby may contribute to shorter postoperative survival following tumor resection.
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PMID:Pancreatic cancer: the potential clinical relevance of alterations in growth factors and their receptors. 883 68

A characteristic feature of colorectal cancer genesis is its stepwise progression, which offers unique possibilities for studying its development. There are two principal kinds of mutation leading to uncontrolled cell proliferation and cancer. The first renders a stimulatory gene hyperactive--generation of an oncogene--and the second is the inactivation of a tumour suppressor gene. Current knowledge suggest that the change from normal mucosa to a small adenoma may be mediated by mutations of the APC gene and MCC gene on chromosome 5, by chromosome 5 deletion, by c-myc activation, and by DNA hypomethylation. The development to a large adenoma may be caused by Ki-ras mutation and further change to a dysplastic adenoma by deletion of the DCC gene on chromosome 18. The ability to become an invasive carcinoma may then be mediated by p53 mutations and deletion of chromosome 17p. Identification of genetic markers for metastatic disease is under progress.
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PMID:Genetic aspects of colorectal cancer: the surgeon's view. 889 51

Genetic instability, alterations of tumor suppressor genes as well as activation of oncogenes and aberrant expression of growth factor/receptor system found in human stomach carcinogenesis are overviewed. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and amplification of the cyclin E gene are common events of both well differentiated and poorly differentiated gastric carcinomas. K-ras mutations, c-erbB2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC, LOH of the bcl-2 gene and LOH at DCC locus are preferentially associated with well differentiated gastric cancer. On the other hand, microsatellite instability, reduction or loss of cadherin and catenins, K-sam and c-met gene amplification confer the development and progression of poorly differentiated or scirrhous gastric carcinomas. Interaction between cell-adhesion molecules in the c-met expressed cancer cells and hepatocyte growth factor from stromal cells is involved in morphogenesis of gastric cancer.
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PMID:[Multistep stomach carcinogenesis]. 892 Jun 75

Though colorectal tumorigenesis has long been thought to be a multistep mechanisms, recently has it become possible to identify the molecular events that underlie the initiation and progression of colorectal carcinoma. Though the analysis of mutations in colorectal tumors at various stages of their development allows definition of a model for colorectal tumorigenesis, because the progression is the result of a series of genetic changes that accumulate activation of oncogene (K-ras), inactivation of tumor-suppressor gene (two-hit mutation of APC, Pla2s, p53, suppressor gene on chromosome 8p22 locus, NF2 and DCC) and mismatch repair gene (hMSH2, hMLH1 hPMS family and TGF beta II receptor linked DNA repair). These accumulation of genetic alterations contribute to tumor development and/or progression in primary colorectal carcinoma.
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PMID:[Genetic steps in colorectal cancer]. 892 Jun 76


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