A importância do gene p53 na carcinogênese humana

Revista Brasileira de Hematologia e Hemoterapia 01/2002; DOI: 10.1590/S1516-84842002000200004
Source: DOAJ

ABSTRACT Existem várias razões que justificam o título de "guardião do genoma" do gene P53. Seu envolvimento, direto ou indireto, tem sido observado na etiopatogenia de praticamente todas as neoplasias humanas, incluindo as leucemias e linfomas. Conhecer seus mecanismos de ação é fundamental para compreender os aspectos moleculares da carcinogênese. O presente trabalho apresenta uma revisão sobre as características deste gene e sua importância no diagnóstico, prognóstico e terapêutica, o que faz dele um alvo em potencial das estratégias de terapia gênica.

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    ABSTRACT: The p53 gene encodes a protein that has molecular weight of 53kD and is also called p53 protein, being constantly studied for its classic concept of "genome guardian". This gene plays a range of essential functions to ensure the cell cycle control, in addition to playing a central role in carcinogenesis. With respect to neoplasias, it prevents the neoplastic transformation through three intricate mechanisms. Depending on the extent of the mutation, different responses may be sent by p53 and those range since the disruption of the cell cycle, the correction of the mutation through the activation of repair proteins or still, the induction of senescence or cell death by apoptosis. This review aims to address the structural and functional aspects of the p53 gene and protein, and also reaffirm their participation in the carcinogenesis control, approaching their major mutations and the anticancer gene therapy involving this gene. revisão visa a abordar os aspectos estruturais e funcionais do gene p53 e proteína, e também reafirmar a sua participação no controle da carcinogênese, abordando suas principais mutações e a contribuição para a terapia gênica anticâncer. Palavras-chave: mutações, neoplasia, geneterapia, p53.
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    ABSTRACT: The saffron (Curcuma long Linn) is a herbaceous perennial, rizomatosa, belonging to the family Zingibe- raceae and classified as condimental plant. The curcumina is the main dye present in the cúrcuma rhi- zomes. Besides being used as a dye and condiment, it presents antioxidants and antimicrobial sub- stances, which bring to it the possibility of employment in the fields of cosmetics, textile, medical and food. The healing and anti-inflammatory effects, as well as the ability to induce apoptosis and sequester free radicals are also recognized. However, there are major controversies with respect to carcinogenesis of this species. Taking this into consideration, this study aimed at assessing the carcinogenic potential of saffron through the test for the detection of tumor (wts) in Drosophila melanogaster. This way, three solutions were prepared from aqueous saffron, in concentrations: 1mg/mL, 3mg/mL, 5mg/mL. The treatment was conducted with all the larvae descending from the intersection of wts/TM3 females with males mwh / mwh. The results showed that the saffron presents carcinogenic potential in the concen-
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    ABSTRACT: Penile carcinoma constitutes up to 16% of male malignancies in developing countries. Changes in the p53 and murine double minute 2 pathway are important events in various cancers. Associate alterations in murine double minute 2 and p53 expression were evaluated by molecular techniques, with the clinical data of 297 cases of penile carcinoma. Automated immunohistochemistry was performed for murine double minute 2 and p53 using the primary antibodies SPM14 and DO7, respectively. Fluorescent in situ hybridization was performed using the probes murine double minute 2 at 12q15 and TP53 at 17p13.1. Slides were digitalized, and bright-field and fluorescent images were analyzed. TP53 was sequenced in 16 cases. The expression of p53 was higher in poorly differentiated, infiltrative border, corpus spongiosum, corpora cavernosa, and invasive urethral carcinomas. Patients who died of disease also expressed higher levels of p53. p53-negative tumors were associated with higher overall survival. Murine double minute 2 showed no difference of expression in any group of tumors, no correlation with p53 expression. No alterations in genes or chromosomes were observed. Mutations in TP53 were observed in 4 of 16 cases: p.T170M, p.L252P, p.C176Y, and the novel ☆ Funding: The study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo. J. V. and F. A. S. are researchers of the Conselho


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