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Involvement of splicing variants of TRIM37, BRRN1 and MK-STYX genes in breast cancer

Grant number: 09/02457-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2009
Effective date (End): April 30, 2013
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Dirce Maria Carraro
Grantee:Tatiana Iervolino Ricca
Home Institution: Hospital A C Camargo. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
Associated research grant:08/57887-9 - National Institute of Oncogenomics, AP.TEM

Abstract

Evidences have been showing that alternative splicing occurs in at least 95% of human genes which increase the proteomic diversity, as 80% of these events occur within the coding region. Some splicing variants are preferentially expressed in human tumors and can be potential molecular markers for more accurate diagnostic and prognostic factors, as well as therapeutic targets. The aim of this study is to identify over expressed splicing variant in breast tumor and test them as molecular markers. For that, 270 exons previously identified as over expressed in tumor tissues by in silico analysis were selected, immobilized onto nylon membranes and interrogated by 31 tumor and 11 normal breast samples. This analysis showed 14 exons over expressed in breast cancer. Through validation by qRT-PCR, 3 of them, TRIM37, MK-STYX and BRRN1, fulfilled stringent criteria revealing to be prone splice variants containing breast tumors-associated exon 23, 5 and 5, respectively, using the initial and an independent set of 40 tumor breast samples. Correlation of transcripts expression with clinical and histopathological data reported positive associations between the expression of the TRIM37 splice variant containing exon 23 inclusion and the presence of estrogen and progesterone receptors, as well as the absence of p53 mutation. These associations were not observed when the expression of TRIM37 variant skipping the same exon was analyzed, indicating that they are related to the presence of the exon 23. Additionally, the protein product from TRIM37 exon 23 inclusion variant showed remarkable imbalance in expression level when the total protein content of tumor and normal breast cell lines were assessed using anti-TRIM37 antibody, suggesting that this isoform may be functionally important in the context of breast cancer.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SENS-ABUAZAR, CAROLINA; NAPOLITANO E FERREIRA, ELISA; BUENO TOLEDO OSORIO, CYNTHIA APARECIDA; VICTORINO KREPISCHI, ANA CRISTINA; RICCA, TATIANA IERVOLINO; CASTRO, NADIA PEREIRA; DA CUNHA, ISABELA WERNECK; MACIEL, MARIA DO SOCORRO; ROSENBERG, CARLA; BRENTANI, MARIA MITZI; SOARES, FERNANDO AUGUSTO; ROCHA, RAFAEL MALAGOLI; CARRARO, DIRCE MARIA. Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast. TRANSLATIONAL ONCOLOGY, v. 5, n. 2, p. 113-U105, APR 2012. Web of Science Citations: 7.

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