Characterization of MTAP gene expression in breast cancer patients and cell lines

Sarah Franco Vieira De Oliveira, Monica Ganzinelli, Rosaria Chilà, Leandro Serino, Marcos Euzébio Maciel, Cícero De Andrade Urban, Rubens Silveira de Lima, Iglenir João Cavalli, Daniele Generali, Massimo Broggini, Giovanna Damia, Enilze Maria De Souza Fonseca Ribeiro

Research output: Contribution to journalArticlepeer-review

Abstract

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 tumors̈ 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.

Original languageEnglish
Article numbere0145647
JournalPLoS One
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 11 2016

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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