[The p53 gene and protein in bronchial carcinogenesis:from biological to clinical aspects].
The p53 gene codes for a nuclear phosphoprotein which is capable of modulating the expression of certain genes implicated in the regulation of cell division. The mutation of an allele on the p53 gene with loss of the healthy allele, in different tissues such as lung, larynx, bladder, liver, skin, colon and breast, which may or may not be exposed to chemical or physical carcinogens (tobacco, radon, ultraviolet, aflatoxin B1), is associated with the occurrence of cancer. Indeed, the mutated p53 protein loses its anti-proliferative properties favouring a de-regulation of cellular multiplication with the accumulation of genetic aberrations. The homozygous deletion of the p53 gene in germ cells in the members of certain family cancers (Li-Fraumeni syndrome) leads to an increased incidence of cancers in the child or young adult. The most frequent mutations of the p53 gene end in a stabilisation of the mutated protein with immuno-histochemical nuclear marking of the cells carrying such an alteration. In certain patients this stabilisation of the mutated protein ends in auto-immunisation with anti-p53 serum antibodies. Bronchial cancer is a cancer of which the mutations of p53 are the most frequent (45-65% of bronchial cancer) as result of the mutagenic effect of tobacco smoke. These mutations seem to be associated with a bad prognosis and indeed to chemo-and radiotherapeutic resistance. The early diagnosis of p53 alterations (in dysplastic lesions or tumours which are only slightly developed) would enable new therapeutic interventions in bronchial cancer such as gene therapy or radio-immunotherapy to either restore the p53 gene to normality or to eliminate the cells expressing the mutated p53 protein respectively.
Zalcman
G
G
Service de Pneumologie, Hôpital Saint-Louis, Paris.
Trédaniel
J
J
Lechapt
E
E
Lubin
R
R
Soussi
T
T
Hirsch
A
A
D000483:Alleles; D002283:Carcinoma, Bronchogenic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D011836:Radiation Tolerance; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53
Le gène et la protéine p53 dans la carcinogenèse bronchique: de la biologie à la clinique.