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

While most authors currently classify dural-based hemangiopericytoma (HPC) as a distinct entity rather than as a subtype of meningioma, the histogenesis of HPC has long been debated. We have recently shown that meningiomas contain frequent mutations of the neurofibromatosis 2 gene, while HPCs do not, suggesting that HPC is genetically distinct from meningioma. In the present study, we evaluated a series of 31 dural HPCs (including 3 pairs of primary and recurrent tumor) and 26 meningiomas for alterations in the cell-cycle regulatory genes CDKN2/p16 and p53. Homozygous deletions of the CDKN2/p16 gene were detected using a comparative multiplex polymerase chain reaction assay in 7 of 28 primary HPCs (25%), but in only one of 26 meningiomas (P = 0.03). Among the HPCs with recurrence, 1 pair of 3 had a homozygous CDKN2/p16 deletion. The 1 meningioma with a CDKN2/p16 deletion was a meningothelial meningioma, without atypical or malignant features. Single-strand conformational polymorphism analysis of all three exons of CDKN2/p16 and exons 5-8 of p53 revealed no mutations in either HPCs or meningiomas. These results illustrate that homozygous deletions of CDKN2/p16 occur in HPCs and suggest that alterations of the p16-mediated cell-cycle regulatory pathway may underlie the formation or progression of some HPCs. The data also provide further genetic evidence that HPC is not a subtype of meningioma.
 ...
PMID:Homozygous deletions of the CDKN2/p16 gene in dural hemangiopericytomas. 883 33

Exons 1-3 of the p16/CDKN2 gene, exons 4-9 of the p53 gene and exons 1 and 2 of H-, K- and N-ras genes were screened for mutations by a combination of immunohistochemistry and single-strand conformational polymorphism (SSCP) analyses of polymerase chain reaction products from human surgical samples of both frank oral squamous cell carcinomas and premalignant lesions. The samples included 20 squamous cell carcinomas, 10 epithelial dysplasias and 10 epithelial hyperplasias. No identifiable gene mutations were detected in any of the dysplasias or hyperplasias, while 2 (10%) deletions and 2 (10%) mutations of p16/CDKN2, along with 5 (25%) p53 mutations were found in the advanced carcinomas, yielding characteristic p16/ CDKN2 and p53 changes. A mutation in the K-ras gene was found in single carcinoma and dysplastic samples. From the data, it can be argued that p16/CDKN2 and p53 mutations are relatively late occurrences in human oral tumorigenesis and that genetic alterations of the ras genes may not play a significant role in squamous neoplasia.
 ...
PMID:Alterations of p16/CDKN2, p53 and ras genes in oral squamous cell carcinomas and premalignant lesions. 883 20

The cell cycle regulatory proteins p16 and p21 cause cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D-CDK4 complexes. The TP53 gene, regulating the p21 protein, is mutated at high frequency in ovarian cancer. The CDKN2 gene, encoding the p16 protein, has been mapped to chromosome 9p21 and encompasses three exons. To establish the frequency of CDKN2 gene abnormalities in ovarian tumour specimens, we have studied this gene in five ovarian cancer cell lines and in 32 primary and five metastatic ovarian adenocarcinomas. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing techniques both exon 1 and 2 of the CDKN2 gene, encompassing 97% of the coding sequence, were analysed. In addition, the TP53 gene was studied for the presence of mutations. The cell line HOC-7 showed a 16 bp deletion in exon 2 of the CDKN2 gene, resulting in a stop codon, whereas in cell line SK-OV-3 this gene was found to be homozygously deleted. Nine primary tumour specimens showed a migration shift on SSCP. Sequencing revealed a common polymorphism (Ala148Thr) in seven of these ovarian tumour specimens. The two other tumour samples were found to contain silent mutations, one at codon 23 (GGT-->GGA) and the other at codon 67 (GGC-->GGT). Mutations in the TP53 gene were observed in 46% of the ovarian tumour specimens. We conclude that CDKN2 gene alterations are rare events in human ovarian cancer. The low prevalence of these alterations do not allow for analysis of an association of this gene with prognosis.
 ...
PMID:Sporadic CDKN2 (MTS1/p16ink4) gene alterations in human ovarian tumours. 885 76

An understanding of the biological significance of the multiple genetic alterations identified in clinical bladder cancers to the stepwise pathogenesis of the disease is evolving. Alterations in p53 and pRb, products of the chromosomes 17p13 TP53 and 13q14 RB tumor suppressor genes, occur in approximately 50% and approximately 33% of bladder cancers respectively, and are associated with later stage, higher grade disease. p53 and pRb alterations are also known to occur in early stage bladder carcinoma in situ where they are thought to represent a poor prognosis for tumor progression. Allelic loss of genes on 9p21 occurs in approximately 50% of bladder cancers, but whether the only critical gene in this region is the CDKN2/p16 cyclin/CDK inhibitor is at present uncertain. Amplification and/or overexpression of the oncogenes epidermal growth factor receptor and erbB2 are associated with later stage disease. Finally, recent findings generated using in vitro transformation systems with human uroepithelial cells provide strong evidence that loss of genes on 3p, which occurs in approximately 20% of bladder cancers, and/or gain of genes on 20q play an important role in blocking HUC cellular senescence. This latter phenotype should represent a critical step in oncogenesis, as cells that do not senesce can survive to accumulate the multiple genetic alterations associated with invasive and metastatic bladder cancers. Further understanding of the biochemical mechanisms underlying these genetic changes will provide the additional information needed to design better strategies for bladder cancer intervention and treatment.
 ...
PMID:A molecular genetic model of human bladder cancer pathogenesis. 889 68

The p16INK4a was isolated as a gene which binds and inhibits the cyclin-dependent kinase 4. Other laboratories reported that the isolated gene frequently homozygously deleted within chromosome 9p21 was the p16INK4a. The p16INK4a gene was thought be a hot gene like the p53 gene at the time. Nevertheless, the gene was thought to be a false tumor suppressor gene due to the low incidence the alterations of the gene in various surgical tumor samples. Since then, there have been a lot of reports supporting that p16INK4a is a really tumor suppressor gene including the reports on the high incidence of p16INK4a alterations in some kinds of tumors, on the higher incidence of p16INK4a alterations in the metastatic tumors than that of the primary tumors, on the G1 arrest of p16INK4a lack cells transfected with p16INK4a cDNA, and on the inactivation of p16INK4a gene by hypermethylation. Therefore, the p16INK4a gene has become the tumor suppressor gene, lately. Moreover, the INK4 family including p15INK4b, p18INK4c, and p19INK4d was isolated. These reports taken together, p16INK4a and INK4 family might play important roles in the genesis and development of cancer.
 ...
PMID:[Molecullar structure and function of the p16/INK4a/CDKN2/MTS1 and the INK4 family, and their association with carcinogenesis]. 892 Jun 70

Various molecular genetic abnormalities have been reported in esophageal carcinoma. These include amplification of the chromosome 11q13 region containing cyclin D1, EXP1 and EMS1 genes, and the oncogenes, the epidermal growth factor receptor gene, EGFR/c-ERBB1, and c-myc. Loss of heterozygosity (LOH) at several chromosome loci and point mutation of the p53 and p16/CDKN2 tumor suppressor genes have also been described. Mutations of p53 gene and LOH at 3p and 9q loci were investigated in esophageal epithelial dysplasia. In contrast, amplification of cyclin D1, EGFR, c-myc and other genes was accumulated in advanced tumors with invasion. Cyclin D1 amplification is found more in metastatic lesions than in primary tumors.
 ...
PMID:[Genetic events during development of esophageal squamous cell carcinoma]. 892 Jun 74

Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles. Genetic alterations affecting p16(INK4a) and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein (RB) and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development. Like the tumor suppressor protein p53, components of this "RB pathway," although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life.
 ...
PMID:Cancer cell cycles. 893 49

Understanding the growth constraints imposed on normal human melanocytes may help to elucidate the processes conferring growth advantage to melanoma cells. Several synergistic growth factors have been identified for normal human melanocytes. They include fibroblast growth factors (FGF), hepatocyte growth factor/scatter factor, mast/stem cell growth factor, and the neuropeptides endothelin-1, 2 and 3 (ET-1, ET-2, ET-3). From this group of peptides, only basic FGF (bFGF/FGF2) appears, so far, to play a role in autonomous growth of melanoma cells. Aberrant expression of FGF2 is due to activation of an otherwise repressed gene by a mechanism that may involve the transcriptional activity of wild-type p53. The growth factors and activated receptors aberrantly expressed in melanoma cells act in concert with molecules that control cell cycle progression. These proteins bind to, and regulate cyclin-dependent kinase (CDK), such as CDK4, responsible for phosphorylation of retinoblastoma (RB) and dissociation of RB-E2F1 inhibitory complexes, thereby allowing progression through the cell cycle. Constitutive CDK4 activity in melanomas may be the results of inactivation of the negative regulators known as CDK inhibitor p16INK4, and/or p21; and/or overexpression of cyclin D, the positive CDK4 regulator. This complex set of changes in melanoma cells can lift growth constraints by inducing unregulated expression of genes promoting transition from GI to S phase of the cell cycle.
 ...
PMID:Growth factors and melanomas. 897 May 86

p16INK4 protein (p16) and retinoblastoma protein (pRB), like p53 protein, are important tumor suppressors that regulate the cell cycle. We immunohistochemically examined fresh-frozen specimens of 114 resected non-small cell lung cancers (NSCLCs) for loss of p16 and pRB expression, together with aberrant accumulation of p53 protein and the proliferative activity determined by the Ki-67 index. Three pRB-positive tumors were uninterpretable for p16 status. Of the remaining 111 tumors, 30 (27%) lacked p16 expression, and 10 (9%) lost pRB expression. No tumors showed coincident loss of both proteins, supporting the hypothesis that they function in a single pathway. Of 25 tumors, including 4 p16-negative tumors, examined by Southern blot analysis, only 2 p16-negative tumors were considered to have reduced gene dosage consistent with possible homozygous deletion of the CDKN2 gene encoding p16, suggesting that immunohistochemistry is a sensitive and suitable method to screen for p16 alteration. Loss of p16 expression did not correlate with any clinical factors or p53 status, whereas loss of pRB expression correlated with heavy smoking (P = 0.03 by Fisher's exact test and P = 0.01 by the multivariate logistic regression analysis). Proliferative activity was considerably higher in p53-positive tumors than in p53-negative tumors (P < 0.001). Loss of p16 or pRB expression was associated with a further increase in proliferative activity in the p53-positive tumors (P = 0.009) but not with proliferative activity in the p53-negative tumors. These results suggest that alteration of the p16/pRB pathway is relatively frequently involved in the development and progression of NSCLCs and that its effect on the proliferative activity is potentially synergistic with altered p53 protein.
 ...
PMID:Altered p16INK4 and retinoblastoma protein status in non-small cell lung cancer: potential synergistic effect with altered p53 protein on proliferative activity. 897 Nov 52

The recently discovered p15INK4B and p16INK4 genes encoding cell cycle regulating proteins, map to a region on chromosome 9p21 that is commonly deleted in a variety of malignant diseases. The p16INK4 gene has now been shown to be a tumor suppressor gene. It is frequently inactivated in cancer and is possibly the second most often mutated gene in human malignant disease after p53. The role of the p15INK4B and p16INK4 genes in hematologic malignancies has been the subject of intense investigation since their discovery. In this review we address the function and possible role in tumorigenesis of the p15INK4B and p16INK4 genes and discuss their significance as prognostic markers in hematologic malignancies.
 ...
PMID:Inactivation of the p15INK4B and p16INK4 genes in hematologic malignancies. 903 Nov 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>