The predominant stromal cell type in breast carcinomas is the fibroblast. These fibroblasts are phenotypically different from their normal counterparts and they present several altered features such as proliferative potential, expression of growth factors and production of different ECM proteins. Moreover tumor environmental is involved in angiogenesis and invasion. Thus, fibroblasts may be a critical impact on various therapeutic strategies and also should be considered as potential targets of anti tumor treatment. However few genes involved in this interaction have been described. Our main goal in the present work is analyzing the molecular mediators of the heterotypic signaling interactions between epithelial cells and fibroblasts. Specifically, human breast tumor tissues are available from breast cancer surgery, enabling the establishment of fibroblasts primary cultures. Otherwise, fibroblasts can be obtained by laser dissection. Our first step is to quantify individual gene expression in RNA extracted from fibroblasts of tumors obtained from patients at different clinical stages by serial analysis of gene expression (SAGE) and compare the gene pattern obtained with that measured in RNAS of fibroblasts obtained from mammoplasties. Once candidate genes have been identified, their differential expression will be validated by real time PCR. Chromosomal imbalance will be determined by comparative genomic hybridization (CGH). (AU)
Articles published in Pesquisa FAPESP Magazine about the research grant:
ROZENCHAN, PATRICIA BORTMAN;
CARRARO, DIRCE MARIA;
DE CARVALHO MOTA, LOUISE DANIELLE;
BASTOS, ELEN PEREIRA;
NAPOLITANO E FERREIRA, ELISA;
TORRE, CESAR H.;
HIRATA KATAYAMA, MARIA LUCIA;
ROELA, ROSIMEIRE APARECIDA;
LYRA, EDUARDO C.;
SOARES, FERNANDO AUGUSTO;
AZEVEDO KOIKE FOLGUEIRA, MARIA APARECIDA;
GUEDES SAMPAIO GOES, JOAO CARLOS;
BRENTANI, MARIA MITZI.
Reciprocal changes in gene expression profiles of cocultured breast epithelial cells and primary fibroblasts.
International Journal of Cancer,
DEC 15 2009.
Web of Science Citations: 41.