Article

A importância do gene p53 na carcinogênese humana

Revista Brasileira de Hematologia e Hemoterapia 04/2002; 24(2). 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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    • "TP53 is essential for the growth, development, and differentiation of normal cells and ensures genomic stability [3] [4]. This tumor suppressor gene is one of the most important genes of tumorigenesis because mutations in this gene exist in more than 50% of all cancers [5] [6]. Such mutations often result in the overexpression of p53 protein containing alterations that impede its normal function [3]. "
    [Show abstract] [Hide abstract] 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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    • "TP53 is essential for the growth, development, and differentiation of normal cells and ensures genomic stability [3] [4]. This tumor suppressor gene is one of the most important genes of tumorigenesis because mutations in this gene exist in more than 50% of all cancers [5] [6]. Such mutations often result in the overexpression of p53 protein containing alterations that impede its normal function [3]. "
    [Show abstract] [Hide abstract] 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 c.803_810del8; these changes correlated with p53 expression by immunohistochemistry. Murine double minute 2 is not useful in the prognosis of penile carcinoma by immunohistochemistry. Additional studies on the transcriptional, posttranscriptional, and epigenetic aspects are necessary to understand the interactions between p53 and murine double minute 2 because we did not observe any numeric alterations by fluorescent in situ hybridization. Examining p53 is helpful in identifying patients with more aggressive tumors and may be crucial in selecting the most suitable surgical procedure.
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    [Show abstract] [Hide abstract] 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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