| Autor: |
de Oliveira SF; Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil., Ganzinelli M; Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche ''Mario Negri', Milan, Lombardia, Italy., Chilà R; Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche ''Mario Negri', Milan, Lombardia, Italy., Serino L; Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil., Maciel ME; Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil., Urban Cde A; Department of Mastology, Breast Unit, Hospital Nossa Senhora das Graças, Curitiba, Paraná, Brazil., de Lima RS; Department of Mastology, Breast Unit, Hospital Nossa Senhora das Graças, Curitiba, Paraná, Brazil., Cavalli IJ; Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil., Generali D; Laboratorio di Oncologia Molecolare Senologica, U. O. Multidisciplinare di Patologia Mammaria, A. O. Istituti Ospitalieri di Cremona, Cremona, Lombardia, Italy., Broggini M; Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche ''Mario Negri', Milan, Lombardia, Italy., Damia G; Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche ''Mario Negri', Milan, Lombardia, Italy., Ribeiro EM; Department of Genetics, Federal University of Paraná, Curitiba, Paraná, Brazil. |
| Abstrakt: |
MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors´ MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNBC. |
