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)

In this preliminary series, the product of the tumour suppressor gene p53 was detected in 12/15 cases of oral squamous cell carcinoma (SCC) and in two cases of leukoplakia. The tumours either expressed the mutant form of p53 throughout the specimen or contained focal areas of positive cells. p53 expression was commonly observed in tumours obtained from patients who were heavy smokers and drinkers suggesting that alterations in the p53 gene may be one of the sites of genetic damage in this group of patients.
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PMID:Expression of the tumour suppressor gene p53 in oral cancer. 843 18

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. The purpose of this study was, therefore, to determine the role of alterations of the tumour suppressor gene p53, and the proliferation status of the lesions determined by PCNA expression. We investigated p53 and PCNA expression in 265 tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oral mucosa by immunohistology. Quantitative analysis showed a gradual increase in PCNA expression from normal mucosa to moderately differentiated SCC. p53 expression was detectable in benign premalignant lesions. The increase in the number of p53-positive biopsies was correlated with the dysplasia and loss of differentiation in the premalignant and malignant lesions.
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PMID:p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa. 874 74

Carcinogenesis is a multi-step process including aberrant expression of two interacting classes of genes--oncogenes and tumour suppressor genes. With recent technological advances, it is feasible to identify the various molecular lesions underlying the different stages of neoplasia. Squamous cell carcinomas of the head and neck, although representing 2-4% of the malignancies in the West, comprise a large fraction (40%) of total cancers in India, posing a major health problem. Further, epidemiological and experimental evidence unequivocally confirms a causal association between tobacco chewing habit, highly prevalent in India, and oral cancers. Thus, the oral cancers offer an excellent in vivo system for the study of the environmental tobacco-carcinogen induced molecular alterations in the malignancy, and associated premalignant lesions such as leukoplakia. With a view to elucidating the molecular lesions involving oncogenes in oral carcinogenesis, we have investigated myc/ras/EGF-R activation by amplification, point mutation, gene rearrangement and allelic losses. Further, a functionally activated potent transforming gene was detected in a NIH3T3 transfection/tumorigenicity assay, unrelated to myc/ras/EGF-R. Studies on the involvement of p53 gene in oral cancer, indicates p53 allelic loss as an event observed in leukoplakia and tumour tissues. Advanced oral cancer stages demonstrate cumulative molecular aberrations, with greater than 95% samples showing oncogene involvement, thus indicating a multi-step process of oral carcinogenesis. The review presents a comparative picture of the oral malignancies seen in Western countries and India, significance of molecular lesions and future perspectives of oncogenes and tumour suppressor gene involvement in oral cancer.
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PMID:Molecular lesions in human oral cancer: the Indian scene. 791 88

A microsatellite assay was used to screen 31 potentially malignant oral lesions presenting as leukoplakia and erythroplakia, with histological evidence of dysplasia, for genetic abnormalities at loci which frequently show allelic imbalance when oral squamous cell carcinomas (SCC) are examined. The microsatellite and restriction fragment length polymorphism (RFLP) markers selected were at 3p21, 8p21-23, 9p21 and included sequences within the Rb (13q14.2), p53 (17p13.1) and DCC (18q21.1) tumour suppressor genes. 8 patients subsequently developed an invasive tumour at the same site, or within 2 cm of the premalignant lesion. A further 8 patients developed SCC at a distant site. Seventy-seven per cent (24/31) of these potentially malignant lesions showed allelic imbalance (AI) and 55% (17/31) of cases showed microsatellite instability (msi). The probability of developing SCC was much greater for patients with lesions showing AI at two or more relevant loci (P = 0.008 by the logrank test) than the group with AI at fewer loci. The estimated probability of development of SCC in this group by 5 years was 73% (95% Cl: 50-92%). This suggests that determining the number of genetic abnormalities in a potentially malignant lesion can help identify patients with true precancers who should be followed closely to ensure that they receive chemoprevention and appropriate advice to limit risk factors, and to allow the early detection of invasive lesions.
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PMID:Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer. 968 68

Alterations in p53 tumour suppressor gene and its expression may be implicated in the pathogenesis of betel- and tobacco-related oral cancer. There is wide regional variation in betel- and tobacco-consuming habits in different parts of the Indian subcontinent. The purpose of this study was to determine the correlations between p53 gene mutations, protein accumulation and serum antibodies in oral precancer and cancer. We analysed 30 potentially malignant oral lesions (leukoplakia) and 30 oral squamous cell carcinomas (SCCs) from northern India because the betel quid-consuming habits are different from those prevalent in other regions of India. p53 mutations were analysed by polymerase chain reaction amplification of genomic DNA and direct sequencing, p53 protein accumulation by immunohistochemical analysis and circulating p53 antibodies by ELISA. p53 gene mutations, analysed within exons 5-9, were observed in five out of 30 (17%) potentially malignant oral lesions and seven out of 30 (23%) oral SCCs. All the mutations were base substitution mutations. Three missense and two nonsense mutations were observed in potentially malignant oral lesions, while six missense and one nonsense mutations were identified in oral SCCs. The probable hot spots for the mutations were identified at codons 126, 136 and 174, which have not been observed thus far. A good correlation was observed between p53 missense mutation, p53 antibodies and p53 protein accumulation in matched potentially malignant and malignant oral lesions. All the potentially malignant and cancerous lesions harbouring missense mutations showed accumulation of p53 protein and the majority of these patients showed circulating p53 antibodies suggesting that serological detection of p53 antibodies may serve as a surrogate marker for p53 alterations in oral lesions.
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PMID:Correlation between p53 gene mutations and circulating antibodies in betel- and tobacco-consuming North Indian population. 1128 78