Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to identify tumor suppressor genes whose inactivation is associated with the acquisition of metastatic ability in colorectal carcinoma. The results indicate that a specific subset of tumor suppressor genes is involved in metastasis of colorectal carcinoma. First, both the p53 and DCC genes were altered in 100% of liver metastases. Second, the incidence of loss of heterozygosity (LOH) at loci on chromosomes 13q, 14q, and 18q in liver metastases was higher than in primary tumors. Third, LOH or rearrangement not detected in the primary tumors was observed on chromosomes 13q, 14q and 18q in liver metastases from the same patients, while alterations on chromosome 17p were always detected in both lesions. These observations indicate that concordant inactivation of the p53 and DCC genes and inactivation of several tumor-suppressor genes, especially those on chromosomes 13q and 14q, play important roles in the acquisition of metastatic potential in colorectal carcinoma.
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PMID:[Accumulation of genetic alterations during human tumor progression]. 809 49

Alterations in multiple oncogenes and multiple tumor suppressor genes are observed in human gastro-intestinal cancer. Among them, the most frequently implicated in malignancy and metastasis of esophageal carcinoma may be amplification and overexpression of the human cyclin D gene. In gastric carcinoma, amplification and abnormal expression of the c-met gene encoding receptor for hepatocyte growth factor (HGF) may contribute to the tumor progression and metastasis. Interaction between cadherin in c-met overexpressed tumor cells and HGF from fibroblast may play an important role in morphogenesis of two histological types of stomach cancer. During stomach carcinogenesis the clone having critical p53 mutations may expand selectively to make up a finally advanced stage of malignancy and show metastasis. In colorectal cancer, loss of heterozygosity of the RB, p53 and DCC genes is frequently associated with liver metastasis. Overexpression of nm23 may participate in carcinogenesis and the reduction in nm23 expression is involved in metastasis in gastric and colorectal cancers.
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PMID:[Metastasis related genes and malignancy in human esophageal, gastric and colorectal cancers]. 809 50

To determine if the MCC, DCC or p53 gene is associated with susceptibility to hereditary non-polyposis colorectal cancer (HNPCC), these genes in normal cells from 12 HNPCC patients were analysed by polymerase chain reaction-single strand conformation polymorphism analysis. No changes which may alter the amino acid sequences of these genes were detected, suggesting that these genes are not associated with the susceptibility to HNPCC. Only one of nine HNPCC cancers showed mutations in the MCC and p53 genes on the same analysis. Loss of heterozygosity in chromosomes 5q, 17p, 18q and 22 was detected in four of the nine cancers, all of them being positive as to metastasis to lymph nodes. Abnormalities of the (CA)n repeat were found in six cancers, including all four without metastasis. These data indicate that tumor suppressor genes in chromosomes 5q, 17p, 18q and 22 are associated with the late stage of colorectal tumorigenesis in HNPCC, whereas the (CA)n repeat abnormalities are an early event of tumorigenesis and more essential to HNPCC.
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PMID:DNA alterations in cells from hereditary non-polyposis colorectal cancer patients. 810 46

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

We describe the spontaneous progression of a colon adenoma cell line to tumorigenicity and growth factor independence. This system allows direct comparison of biologic stages of malignant progression with alterations of colon cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line, is at early passages nontumorigenic in the nude mouse, unable to grow in soft agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO-235 daughter passages 93 and higher have in culture spontaneously progressed to being weakly tumorigenic, but retain all other growth characteristics of VACO-235 early passages. A mouse xenograft from late passage VACO-235 was reestablished in culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic, clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles, expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO-411 retains the identical genotype, still expressing only wild type p53. Colonic cells after ras mutation, APC mutation, and DCC inactivation remain nontumorigenic and growth factor dependent. Malignant progression involves at least two additional steps, and in VACO-411 can proceed by a novel pathway not requiring p53 inactivation.
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PMID:A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene. 813 40

Genetic and environmental aspects play an important role in the development of colorectal cancer. However, the common molecular alteration in both hereditary and sporadic colon cancer is localized in the APC gene. the APC gene maps in the long arm of chromosome 5 and was discovered in patients with familial adenomatous polyposis (FAP). The search for the APC gene led to the identification of restriction fragment length polymorphisms (RFLPs) in FAP patients. Using these RFLPs in relatives of FAP patients it is possible to make the presymptomatic and prenatal diagnosis. The FAP syndrome is an interesting model of carcinogenesis in vivo. Thus the different stages involved in the FAP syndrome which include hyperproliferative epithelium, adenoma, adenocarcinoma and metastases, have allowed the analysis of molecular alterations in oncogenes and tumor suppressor genes. The APC gene alteration if not inherited, occurs as the earliest molecular alteration in the development of colorectal cancer whereas structural alterations of the genes myc, ras, p53, MCC and DCC are considered to be late events. All these investigations have lead to 1) a better understanding of the ethiology of cancer and 2) early diagnosis of colorectal cancer in both the hereditary and sporadic forms of the disease.
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PMID:[Molecular genetics of colorectal cancer and carcinogenesis]. 813 31

We immortalized oral keratinocytes by transfecting them with recombinant human papillomavirus (HPV) type 18 DNA and established three cell lines. These lines were morphologically different from their normal counterpart, contained integrated entire HPV-18 DNA, and expressed the viral E6/E7 genes. The cells contained less p53 protein and more c-myc mRNA than normal cells. However, they proliferated only in keratinocyte growth medium (KGM) containing low calcium and were not tumorigenic in nude mice. To test the hypothesis that tumors result from the combined effect of a "high-risk" HPV and chemical carcinogens in the human oral cavity, we exposed the immortalized cells to the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. Three chemically transformed cell colonies were isolated. These cells (a) proliferated well in both KGM and Dulbecco's modified minimum essential medium containing physiological levels of calcium; (b) were capable of proliferating in nude mice; (c) contained intact, integrated HPV-18 sequences; (d) transcribed substantially more HPV-18 E6/E7, transforming growth factor-alpha, and c-myc than the immortalized counterpart; and (e) contained, like the immortalized counterpart, less wild-type p53 protein and DCC message. These data indicate that human oral keratinocytes can be transformed by sequential exposure of normal keratinocytes to a "high-risk" HPV and chemical carcinogens.
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PMID:Combined effects of human papillomavirus-18 and N-methyl-N'-nitro-N-nitrosoguanidine on the transformation of normal human oral keratinocytes. 814 12

In previous studies, we have shown that allelic loss on chromosome 17p, on which the p53 gene is located, is very frequent, and loss-of-function mutations of the p53 gene are closely associated with the tumorigenesis of esophageal cancer. In this study, we performed allelotype analysis to investigate whether other tumor suppressor genes are also involved in esophageal cancer. Using 55 polymorphic DNA markers covering every autosomal arm except 13p, 21p, and 22p, restriction fragment length polymorphism analysis was performed on 36 esophageal squamous cell carcinomas (ESCs) and their adjacent normal tissue samples. Frequent loss of heterozygosity (LOH) of > 30% of the informative cases was observed on chromosomes 3p (41.1%), 5q (52.6%), 6p (30.4%), 8p (33.3%), 9p (35.7%), 9q (30.8%), 11p (32.4%), 13q (52.7%), 17p (55.2%), 17q (33.3%), 18q (45.7%), and 19q (30.4%). Among these, LOH on 5q, 13q, 17p, and 18q was previously reported in ESC and is considered to involve the APC, RB, p53, and DCC genes, respectively. However, our deletion analysis of chromosome 18q revealed that the region commonly lost did not include the DCC locus, suggesting that a possible tumor suppressor gene on 18q other than the DCC gene is involved in ESC. We screened 60 primary ESC tumors and 20 cultured ESC cell lines for the mutation of the APC gene within a mutation cluster region in exon 15, where the "hot spot" of somatic mutation for colorectal and pancreatic cancers is thought to be. We could not find any mutation despite the high frequency of LOH on chromosome 5q. We also analyzed the relationship between the clinicopathological data and the allelic loss and found that LOH on chromosomes 6p and 13q was associated with poor prognosis.
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PMID:Allelotype analysis of esophageal squamous cell carcinoma. 818 88

In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.
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PMID:Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas. 819 70

The tumor suppressor genes p53, Rb, and DCC were studied in five human oral cancer cell lines (FaDu, SCC-4, HEp-2, 1483, and OEC-M1) and in primary normal human oral keratinocytes (NHOK). All tested cancer lines had similar amount of p53 messages to normal cells, but the cancer lines FaDu and SCC-4 contained significantly higher p53 protein levels than did the normal counterpart. Sequencing p53 cDNA for these cancer cells showed point mutations: In the FaDu cell line, a mutation of CGG to CTG occurred at codon 248; and in the SCC-4 cell line, a mutation of CCC to TCC occurred at codon 151. The HEp-2 and 1483 cancer lines translated very low levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations. Southern and Northern analyses revealed that these cell lines harbored HPV-18 DNA and expressed the viral E6/E7 protein. The OEC-M1 line showed different restriction fragment length polymorphism for the p53 gene compared with other cells, and did not express p53. All oral cancer cell lines except the OEC-M1 cells expressed both phosphorylated and hypophosphorylated Rb proteins. Further, the OEC-M1 line expressed smaller sized hypophosphorylated Rb proteins compared with normal cells. Unlike the other cancer lines, the HEp-2 and OEC-M1 lines also did not contain DCC mRNAs. These data indicate that "high risk" HPV infections and mutations of p53, Rb, and DCC genes are frequently found in oral cancer cells and may be associated with oral cancer.
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PMID:State of p53, Rb and DCC tumor suppressor genes in human oral cancer cell lines. 823 12


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