Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines
| Autor: | Giovanna Damia, Marcos Euzébio Maciel, Cicero Urban, Sarah Franco Vieira de Oliveira, Daniele Generali, Iglenir J. Cavalli, Enilze Maria de Souza Fonseca Ribeiro, Monica Ganzinelli, Rosaria Chilà, Massimo Broggini, Leandro Tamião Rodrigues Serino, Rubens Silveira de Lima |
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| Přispěvatelé: | De Oliveira, Sarah Franco Vieira, Ganzinelli, Monica, Chilà, Rosaria, Serino, Leandro, Maciel, Marcos Euzébio, De Andrade Urban, Cícero, De Lima, Rubens Silveira, Cavalli, Iglenir João, Generali, Daniele, Broggini, Massimo, Damia, Giovanna, De Souza Fonseca Ribeiro, Enilze Maria |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Genetics and Molecular Biology (all)
0301 basic medicine Receptor ErbB-2 lcsh:Medicine Triple Negative Breast Neoplasms Biochemistry 0302 clinical medicine CDKN2A RNA Small Interfering lcsh:Science skin and connective tissue diseases Promoter Regions Genetic Regulation of gene expression Gene knockdown Multidisciplinary Medicine (all) Carcinoma Ductal Breast Adenocarcinoma Mucinous Gene Expression Regulation Neoplastic Organ Specificity 030220 oncology & carcinogenesis Lymphatic Metastasis DNA methylation Azacitidine Adenocarcinoma Female Fluorouracil Receptors Progesterone Research Article Signal Transduction Tumor suppressor gene Antineoplastic Agents Biology 03 medical and health sciences Breast cancer Cell Line Tumor medicine Humans Agricultural and Biological Sciences (all) Biochemistry Genetics and Molecular Biology (all) Cyclin-Dependent Kinase Inhibitor p16 lcsh:R Estrogen Receptor alpha DNA Methylation medicine.disease Carcinoma Lobular 030104 developmental biology Methotrexate Purine-Nucleoside Phosphorylase Cancer research lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 1, p e0145647 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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