Abstract
9593 Background: We have determined the gene profile correlated to doxorubicin resistance in 38 BC patients (pt) treated with primary chemotherapy and 37 genes were differentially expressed in tumors according to response. Among the genes more expressed in sensitive tumors as compared to resistant tumors were ephrin receptor and c-src; JunD; and CDKN2B. Genes more expressed in resistant tumors were fibroblast growth factor receptor 2 and lymphocyte protein TK; Max (Myc partner); and MMP12 (metalloproteinase). We have now analyzed gene expression of these 38 tumors as compared to normal breast tissue (perilesional) obtained from 5 women without cancer submitted to resection of benign lesions. Methods: A tissue specific cDNA microarray glass slide was assembled based on genes expressed in mammary tissue and BC. Genes hyperexpressed in BC as determined in SAGE libraries were also selected. Sequences representing 496 genes and 195 ESTs were chosen in an ORESTES (open reading frame expressed sequence tags) bank (Instituto Ludwig de Pesquisa sobre o Câncer/FAPESP) or synthesized in PCR reactions and spotted 3 or 6 times on glass slides. Tissue was hand dissected, RNA was extracted, amplified, and co-hybridized with a HB4A (normal mammary epithelial cell line) probe against cDNA microarray slides. Results: Median age of BC pt was 51 y; pt were clinically staged as IIA (3), IIB (2), IIIA (17), IIIB (15) and IV (1 pt). Sixty three molecules were differentially expressed between tumors and normal breast tissue. Genes more expressed in tumors included KRT8 and KRT19 (cytoskeleton proteins); MMP11 and MMP12; transmembrane 4 superfamily member tetraspan NET-7; NME2 (tumor suppressor gene); REL (oncogene); MSH2 (DNA repair); XIAP (inhibitor of apoptosis) associated factor 1. Genes more expressed in normal tissue were CCND3 (cyclin D3); KRT14 and KRT15; LAMA3 and LAMB3 (laminin); maspin (proteinase inhibitor); GSTP1 (detoxifying enzyme); ITGB4 (adhesion molecule); JUN, FOS, MYC (transcription factors) and MAX; and ABCG2 (ATP binding cassette). Conclusions: This gene profile seems to characterize breast malignancy. Supported by FAPESP 01/00146–8 No significant financial relationships to disclose.
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