Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S-phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non-tumour cells in minute concentrations, due to its short half-life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat-shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the cells) were present only in high-grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53-positive cells were identified. These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:P53 protein expression in lymphomas and reactive lymphoid tissue. 138 24

Overexpression of the p53 tumour suppressor gene is one of the most common abnormalities in primary human cancers and appears to be a result of point mutation within a highly conserved region of the gene with subsequent encoding for a mutant, more stable protein. In the study, 71 surgically resected hepatocellular carcinomas (HCC) were examined to study the expression of the p53 gene, its relation with clinicopathological parameters and its prognostic significance. Using immunohistochemical detection for mutant p53 protein with monoclonal antibody PAb1801, p53 overexpression was found in 22 tumours (31%) but in none of the non-tumorous liver specimens. Overexpression of p53 was more frequent in tumours with poor cellular differentiation (P = 0.01), in tumours > 5 cm in diameter (P = 0.05), and in those with giant cells present (P = 0.03) and, less significantly, of massive type of Eggel's classification (P = 0.06). It did not have any significant correlation with hepatitis B or C status, background liver disease or serum alpha-fetoprotein levels, nor was it related to tumour invasiveness (venous permeation, direct liver invasion and tumour microsatellite formation). In addition, the presence of p53 mutant protein did not influence tumour recurrence or patients' survival rates. The data suggested that p53 mutation in HCC was associated with a later stage of oncogenesis. However, it was not apparently related to tumour invasiveness/aggressiveness and prognosis.
 ...
PMID:Overexpression of p53 in hepatocellular carcinomas: a clinicopathological and prognostic correlation. 754 99

p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n = 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.
 ...
PMID:Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance. 778 34

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.
 ...
PMID:Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa. 782 4

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53. We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion (P = 0.032) or metastatic disease (P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells (P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells (P = 0.05). Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.
 ...
PMID:Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma. 783 39

The traditional prognostic factors, including stage of disease and tumour grade, have shown a limited prognostic significance and an inability to predict clinical response to specific treatment in patients with laryngeal squamous-cell carcinoma. More recent data suggest that cell kinetics indices, DNA-ploidy, lysosomal cysteine proteinase expression and genetic changes of both tumour suppressor genes and protooncogenes may be considered as reliable and reproducible indicators of biological aggressiveness in these patients. Moreover, the frequency of different genetic alterations suggests that several pathways are involved in the genesis of these neoplasias and, in particular, it is very probable that p-53 expression and PCNA indices (increased in normal mucosa and preinvasive lesions) may constitute more important biomarkers for the early steps of laryngeal carcinogenesis.
 ...
PMID:Biological characterization of laryngeal squamous-cell carcinoma. 869 53

One of the most common cellular gene which negatively regulates the cell cycle, thus functioning as tumour suppressor gene, is the p-53 gene. The presence of this mutated gene has been correlated with, the aggressiveness of several malignant neoplasmas. Expression of the p-53 gene product protein was screened in 55 untreated human germ cell testicular tumours, furthermore a relationship between p-53 expression and clinical resistance was investigated. Using monoclonal antibody and immunoenzyme staining elevated p-53 level could be demonstrated in nuclei of embryonal carcinoma (84%) and seminoma components (56%). Most of the choriocarcinoma cases showed positive staining. Teratomas expressed this antigen negatively or scarcely. In seminomas the highest level of p-53 was stated in stage I. In contrast the opposite tendency could be demonstrated in embryonal carcinomas where p-53 was ++ positive in stage III. Between the high level of p-53 and clinical resistance a converse correlation could be stated because the resistant tumours expressed no or low, the sensitive tumours high level of p-53 protein (P 0.01). These results suggest that elevated p-53 expression could be a prognostic marker of sensitivity in testis cancer.
 ...
PMID:[Correlation between p-53 expression and clinical resistance in testicular cancer]. 872 69

p27Kip is a candidate human tumour-suppressor protein, because it is able to inhibit cyclin-dependent kinases and block cell proliferation. Abnormally low levels of the p27 protein are frequently found in human carcinomas, and these low levels correlate directly with both histological aggressiveness and patient mortality. However, it has not been possible to establish a causal link between p27 and tumour suppression, because only rare instances of homozygous inactivating mutations of the p27 gene have been found in human tumours. Thus, p27Kip1 does not fulfil Knudson's 'two-mutation' criterion for a tumour-suppressor gene. Here we show that both p27 nullizygous and p27 heterozygous mice are predisposed to tumours in multiple tissues when challenged with gamma-irradiation or a chemical carcinogen. Therefore p27 is a multiple-tissue tumour suppressor in mice. Molecular analyses of tumours in p27 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Hence, p27 is haplo-insufficient for tumour suppression. The assumption that null mutations in tumour-suppressor genes are recessive excludes those genes that exhibit haplo-insufficiency.
 ...
PMID:The murine gene p27Kip1 is haplo-insufficient for tumour suppression. 982 98

Several genetic alterations have been implicated in the development of malignant melanoma, but the expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes and their interactions in melanoma have not been completely clarified. We simultaneously examined the expression of p73, c-erbB-2, ras, p53, Mdm2, p27, DCC, hMLH-1, hMSH-2, bcl-2, Bax and NF-kappaB, by immunocytochemistry, in both primary and metastatic melanoma cell lines derived from melanoma patients. p73 was expressed in 7/8 cell lines, but stronger expressed in the metastatic cells than in the primary melanoma cells. c-erbB-2 was detected in all 8 cell lines and ras in 2/5 metastases. p53 was found in all the cell lines and Mdm2 in 1/8 of the cell lines. In the same patient, the intensity of p27 expression was decreased from the primary to the metastatic tumours. bcl-2 was expressed in all the cell lines. Bax was absent in 5/8 cell lines. In the same patient, Bax was weakly expressed in the primary tumour but lacking in the metastases. The data demonstrate that overexpression of p73, c-erbB-2, p53 and bcl-2, and loss of Mdm2 and Bax may interact and play important roles in the development and aggressiveness of human melanoma.
 ...
PMID:Expression of oncogenes, tumour suppressor, mismatch repair and apoptosis-related genes in primary and metastatic melanoma cells. 1171 83

Clear cell renal cell carcinomas (RCCs) are characterized by a deletion of chromosome 3p, which might result in the inactivation of the FHIT (fragile histidine triad) gene, a putative tumour suppressor gene. To explore the relevance of FHIT aberrations for tumour progression and prognosis in clear cell RCCs, FHIT protein expression was analysed in formalin-fixed tissue from 149 clear cell RCCs by immunohistochemistry. FHIT protein expression was found to be markedly reduced in all RCCs, when compared with adjacent non-neoplastic tubule epithelia. Although remaining below the FHIT levels of normal tubule epithelia, a significant increase of FHIT expression became evident from well (G1) to poorly (G3) differentiated clear cell RCCs (p=0.0001) and from low (pT1) to advanced (pT3) tumour stages (p=0.001). The log-rank test demonstrated a significant inverse correlation (p=0.0074) between FHIT expression and tumour aggressiveness as indicated by patient survival. Cox regression analysis revealed that FHIT expression is an independent prognostic parameter (p=0.0139) in clear cell RCCs. In conclusion, clear cell RCCs show a marked reduction of FHIT protein expression when compared with their putative cells of origin. In contrast to other tumour types, however, loss of FHIT protein expression is significantly less pronounced in poorly differentiated RCCs or advanced tumour stages. This versatility of FHIT expression during tumour progression suggests a role for reversible mechanisms of FHIT inactivation during the initiation and progression of clear cell RCCs.
 ...
PMID:FHIT expression in clear cell renal carcinomas: versatility of protein levels and correlation with survival. 1192 Jul 39


1 2 3 4 Next >>