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)

Biliopancreatic malignancy is one of the leading causes of cancer death in the Western world. Defining at risk groups has been difficult. Diabetes mellitus and pancreatitis increase the risk of pancreatic carcinoma, and inflammatory bowel disease and associated sclerosing colangitis increase the risk of biliary tract malignancy. Pancreatic carcinoma has also been described in pedigrees with inherited cancer predisposition. Extensive molecular profiling of pancreatic carcinomas has been accomplished over the past few years, but similar knowledge in other biliopancreatic malignancies is lacking. In almost all pancreas cancers at least one alteration will occur out of a combination of K-ras mutations and inactivation of the tumor suppressor genes p16/MTS1/ink4a, p53 and DPC4/Smad4. Mutations of K-ras and p16 have been described in hyperplastic and dysplastic pancreatic ductal lesions believed to be the non-malignant precursors of pancreatic carcinoma. Detection of K-ras mutations in clinical samples (biliopancreatic secretions, stool, duodenal aspirates, and blood) identical to ones present in primary pancreatic cancers and/or their precursor ductal lesions has been reported in pilot studies. Recently detection of 18q deletions (at the DPC4 locus) in pancreatic secretions from early pancreatic cancers was also reported. These advances raise the possibility that within well defined at risk groups it will be possible to use a combined set of molecular markers to screen clinical samples and detect early pancreatic cancer or even pre-malignant lesions. The fulfillment of this promise will depend on proving the role of molecular screening in decreasing morbidity and mortality, which will require well designed clinical studies.
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PMID:Biliopancreatic malignancy: screening the at risk patient with molecular markers. 1043 11

The MTS1 (Multiple Tumor Suppressor 1) locus is a very original one as its organization results in the expression of two alternative transcripts that encode two structurally and functionally different proteins: INK4a and ARF (also designated p19ARF in mouse and p14ARF in man). Recent findings indicate that the latter is a major component of a regulatory pathway of oncogenic signals culminating in p53 activation by stabilisation of the protein. While the importance of this pathway has been overtly established in animal experimental oncology, it still has to be further documented in human oncology in order for this gene to acquire its full biological significance.
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PMID:[The ARF-p53 pathway: a line of defence against oncogenic signals]. 1085 63

Patients with familial malignant melanoma(FMM) are susceptible for melanoma and multiple dysplastic nevi(atypical mole). FMM is also called as dysplastic nevus syndrome or familial atypical mole and melanoma syndrome. The number of Japanese patients with FMM is very low. In 1994, p16(MTS1, INK4A, CDK4I, CDKN2) gene was cloned as the gene for FMM. p16 gene locus also codes for p14ARF and acts as tumor suppressor through activation of Rb by p16 and p53 by p14ARF. Approximately 20% of FMM patients were shown to carry the germline mutations of p16, indicating the presence of another gene or other genes for FMM, which also may be involved in the development of sporadic malignant melanoma.
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PMID:[Familial malignant melanoma]. 1092 9

Molecular characterization of eight gastric cancer cell lines established in Japan are summarized according to the genetic and epigenetic alterations and growth factor status. TMK-1 poorly differentiated adenocarcinoma cell line harbors mutant p53 tumor suppressor gene and rearrangement of p15MTS2. MKN-1 adenosquamous carcinoma line with mutant p53 reveals silencing of E-cadherin by promoter CpG hypermethylation. MKN-7 well-differentiated adenocarcinoma cell line has amplification of c-erbB2 oncogene and cyclin E gene. MKN-28 well-differentiated adenocarcinoma cell line reveals mutations in p53 and APC tumor suppressor genes and silencing of CD44. The MKN-45 poorly differentiated adenocarcinoma cell line with wild-type p53 is characterized by homozygous deletion of p16CDKN2/MTS1/INK4A and p15MTS2, amplification of c-met oncogene and promoter mutation of E-cadherin. MKN-74 derived from moderately differentiated tubular adenocarcinoma has wild-type p53. KATO-III signet ring cell carcinoma line has genomic deletion of p53, amplification of K-sam and c-met oncogene and mutation of E-cadherin. HSC-39 signet ring cell carcinoma cell line harboring p53 missense mutation has homozygous deletion of p16CDKN2/MTS1/INK4A and p15MTS2, amplifications of c-myc, c-met, K-sam and CD44 gene and mutation in beta-catenin gene.
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PMID:Molecular characteristics of eight gastric cancer cell lines established in Japan. 1110 48

To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/p16 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.
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PMID:Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-heterozygosity on chromosome 16q21-q23 and 9p21-p23. 1119 53

The tumor suppressor gene - p16 INK4/CDKN2/MTS1 and its alternate splice product p14 (ARF), constitute the INK4a locus. We have examined the integrity of exon 1beta of p14(ARF) gene of oral squamous cell carcinomas (n=58) in untreated Indian patients. No mutations were detected in this region by PCR-SSCP analysis of the tumor DNA's. Further, PCR-based analysis revealed homozygous deletions of exon 1beta in 14 of the 58 tumors; these results were confirmed by hybridization of tumor DNAs with exon 1beta specific probe. The deletions were limited to the exon 1beta while the exons coding p16/INK4 were not affected. Except in two cases these deletions were mutually exclusive to the p53 inactivating mutations. These observations suggest an alternate mechanism of loss of p14(ARF) in the genesis of oral squamous cell carcinomas.
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PMID:Selective deletion of p14(ARF) exon 1beta of the INK4a locus in oral squamous cell carcinomas of Indians. 1133 65

We previously demonstrated that approximately one-half of soft-tissue sarcomas were devoid of either pRB, the product of the retinoblastoma gene, or 16, the product of the MTS1/CDKN2 gene, while a smaller subset of aggressive mesenchymal tumors without metastatic potential did not express RB by immunohistochemistry. We now studied the expression of two additional important cell-cycle regulators, namely cyclin D1 and p53, in the same cohort of high- and low-grade lesions. In the aggregate, our data provide a comprehensive overview of the importance of cell-cycle deregulation in mesenchymal neoplasia. Paraffin sections of 58 sarcomas and 23 soft-tissue tumors of low malignant potential (STT-LMP) were reacted with monoclonal antibodies against cyclin D1 and p53, using optimized immunohistochemical staining protocols. The staining data were correlated with expression of pRB and p15 and with a variety of pathologic parameters. A total of 33 of 58 sarcomas (57%) and 9 of 23 STT-LMP (39%) overexpressed p53. Fourteen sarcomas (24%) and 4 STT-LMP (17%) overexpressed cyclin D1. There was no correlation between expression of these two genes and histologic tumor type or grade. Loss of RB and loss of p16 or overexpression of cyclin D1 were mutually exclusive events. Considering all four cell-cycle regulators, sarcomas had a significantly higher abnormality rate than did STT-LMP (P < .005). Only 10% of the sarcomas but 39% of STT-LMP showed normal expression of all four gene products. Based on our findings, overexpression of cyclin D1 and (presumably mutant) p53 appear to be among the most common molecular alterations in human mesenchymal neoplasia, and abrogation of cell-cycle control is observed in the great majority of sarcomas; it is present significantly less frequently in low-grade lesions.
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PMID:Aberrant expression of cell-cycle regulatory proteins in human mesenchymal neoplasia. 1134 47

To study the suppression effect of light rare earth elements (RE) on proliferation of two cancer cell lines. Two cancer cell lines PAMC82 and K562 were used to examine their colony-forming ability in soft agar, microtubule structure, calmodulin levels and regulation of some gene expressions by Northern blot analysis with and without treatment by RE. The results showed that on soft agar culture the colony-forming ability of human gastric cancer cell line PAMC82 treated by RE chloride decreased and the PAMC82 cell microtubule abnormal structure became normal. The calmodulin (CaM) levels decreased in human leukemia cells (K562) treated with cerium chloride and neodymium chloride. The Northern blot analysis revealed marked up-regulation of p53, p16(MTS1), p21 (WAF1) gene expressions in PAMC82 cells treated with lanthanum chloride and cerium chloride, as compared to control PAMC82 cells. The light rare earth elements studied have certain suppression effects on proliferation of cancer cells. This effect might be related to the decrease of calmodulin and up-regulation of some gene expressions in cancer cells.
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PMID:The suppression effect of light rare earth elements on proliferation of two cancer cell lines. 1135 62

The cyclin-dependent kinase inhibitor p16INK4a encoded by the INK4A/CDKN2A/MTS1 gene is a frequent target of 9p21 inactivation in human lung cancers. The p14ARF transcript, which is an alternative spliced form of this locus, is also altered or deleted in a proportion of human lung cancers and has been shown to inhibit cell cycle progression as an endogenous cellular regulator of the p53 protein, raising the possibility that it might constitute an additional lung tumor suppressor gene at the 9p21 locus. To test the candidacy of p14ARF as a lung cancer suppressor and assess the role it plays in radiosensitivity, we transfected the wild-type p14ARF gene into four cell lines which had various endogenous gene backgrounds of INK4A-/p53+/RB+ (A549 and H460), INK4A+/p53+/RB- (H446) as well as p14ARF+/p53-/RB+ (Calu-1). We found that transfection of p14ARF is related to an obvious growth inhibition in all wtp53 cell lines, regardless of INK4A/ARF and RB status. Although it has been shown that p53-induced G1 checkpoint in response to DNA damage by ionizing radiation is p14ARF-independent, we found the radiosensitivity of two p14ARF-deficient cell lines was increased after p14ARF gene transfer. The results indicated that cell cycle redistribution after acquiring the exogenous gene might be the main explanation for the enhanced sensitization. An increased radiation-induced apoptotic proportion in one cell line also suggested a fortified p53 function that might be triggered by the restored p14ARF protein.
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PMID:The exogenous wild-type p14ARF gene induces growth arrest and promotes radiosensitivity in human lung cancer cell lines. 1141 96

We investigated 34 oligodendroglial tumors (7 oligodendrogliomas, 11 anaplastic oligodendrogliomas, 8 oligoastrocytomas, and 8 anaplastic oligoastrocytomas) for deletion, mutation, hypermethylation, and expression of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes at 9p21. One anaplastic oligoastrocytoma carried a homozygous deletion including all 3 genes. None of the tumors demonstrated point mutations in any of the genes. Methylation-specific polymerase chain reaction (MSP) analysis and sequencing of bisulfite-modified DNA, however, revealed frequent hypermethylation of the 5'-CpG islands in CDKN2A, p14ARF, and CDKN2B. Partial or complete methylation of the majority of CpG sites analyzed from each gene was detected in 32% of the tumors at the CDKN2A gene and at a similar percentage (41%) of the tumors at the p14ARF gene and the CDKN2B gene. Most tumors with CDKN2A, p14ARF, and/or CDKN2B hypermethylation either lacked detectable transcripts from these genes or had lower mRNA levels than those determined for non-neoplastic brain tissue. There was a significant correlation between hypermethylation of these genes and the presence of allelic losses on chromosomal arms 1p and 19q. In addition, p14ARF hypermethylation was predominantly found in tumors without a demonstrated TP53 mutation. Taken together, our results indicate that hypermethylation of CDKN2A, p14ARF, and CDKN2B is an important epigenetic mechanism by which oligodendroglial tumors may escape from p53- and pRb-dependent growth control.
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PMID:Oligodendroglial tumors frequently demonstrate hypermethylation of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes. 1176 89


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