Expression d'oncogènes et tumeurs mamaires : étude clinique et développement d'un modèle de souris transgéniques pour v-Ha-ras en toxicologie

Abstract : We have investigated the expression of three oncogenes (c-erbB-2, ras, pS2) and one supressor tumor gene (p53) in first, a clinical study, second, in an experimental one using the v-Ha-ras transgenic mice. Quantification of copy number of c-erbB-2 oncogene has been obtained by gene amplification using non-radioactive amplimer labelling on 29 mammary ductal infiltrating carcinomas. There was an apparent correlation between gene copy number and tumor grade. Immunohistochemistry on the same lesions have shown c-Ha-ras and p53 expression in high grade lesions. pS2 expression was associated to low grade lesions, which confirms the good prognosis associated to this protein. Detection of oncogenes and encoded proteins may be of value for establishing a prognosis of mammary carcinomas. The v-Ha-ras transgenic mice have been used to evidence the carcinogenic potential of chemicals. Using non-radioactive labelling and detection methods (colorigenic and chemiluminescent), we have verified that these mice carried the ras transgene and expressed it in the hematopoietic organs (spleen and thymus) as well as in the kidney and the liver. We have found 2 or 3 copies of the transgene per genome-equivalent. 10 mmol/kg of 2-butoxyethanol administred over 2 weeks using osmotic minipumps have shown that this compound is devoided of epigenetic and genetoxic effects as measured by (i) methylation of total and v-Ha-ras gene DNA, (ii) absence of hydrophobic and hydrophilic DNA adducts. 2-butoxyethanol did not induced tumor formation in the transgenic mice. This animal model could be used as a screening test for possible carcinogenic chemicals
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Aléodjrodo Edorh. Expression d'oncogènes et tumeurs mamaires : étude clinique et développement d'un modèle de souris transgéniques pour v-Ha-ras en toxicologie. Médecine humaine et pathologie. Université Paul Verlaine - Metz, 1996. Français. ⟨NNT : 1996METZ008S⟩. ⟨tel-01777110⟩

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