Biomarcadores moleculares en cáncer de mama
Breast cancer is a disease of high incidence in our country. To decide the best treatment, they are considered proteomic and histological prognostic factors. However, many times the therapy is inadequate; it remains necessary to identify new factors to optimize the diagnosis of disease including its...
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Autores principales: | , , , , |
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Publicado: |
2019
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Materias: | |
Acceso en línea: | https://bdigital.uncu.edu.ar/fichas.php?idobjeto=14757 |
Sumario: | Breast cancer is a disease of high incidence in our country. To decide the best treatment, they are considered proteomic and histological prognostic factors. However, many times the therapy is inadequate; it remains necessary to identify new factors to optimize the diagnosis of disease including its biological aggressiveness and thus determine prognosis and appropriate treatment for the disease. It is also very important to find biomarkers to predict response and customize the antineoplastic treatment. For some years, our group studies the aberrant methylation profile of mammary carcinomas. The results suggest that this profile is specific and exclusive to malignant tumor tissues. In invasive ductal breast carcinomas we report the correlation between aberrant methylation of TP73 gene, the high expression of the deltaN-p73 isoform and a high histological grade, one of the key markers of poor prognosis. The TP73 protein has numerous isoforms that give rise to different biological functions and antagonistic. Not yet been studied whether they modify the sensitivity to conventional treatments used in breast tumors. The proposed objectives are: OBJECTIVE 1: In breast tumors with different clinical-pathological characteristics: a) Determine expression and cellular localization of TA-p73 and deltaN-p73 isoforms b) Correlate expression and localization of p73 isoforms with the tumor aggressiveness. OBJECTIVE 2: In mammary tumor cells with different molecular subtypes: a) Evaluate methylation of both TP73 gene promoters b) Evaluate expression and cellular localization of TA-p73 and deltaN-p73 isoforms. OBJECTIVE 3: Evaluate methylation of the TP73 gene in invasive ductal carcinomas of the breast of patients treated with doxorubicin. To develop the proposed objectives we will use tumor cell lines and human mammary tumor tissues. To determine expression and protein localization, immunohistochemistry and immunofluorescence studies and confocal microscopy will be performed, respectively. To study the methylation of genes, the pyrosequencing methodology will be used. |
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