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Genetic, epigenetic and functional analysis of homeobox genes in oral squamous cell carcinoma

Grant number: 10/08720-4
Support type:Regular Research Grants
Duration: December 01, 2010 - May 31, 2013
Field of knowledge:Health Sciences - Dentistry
Principal researcher:Fabio Daumas Nunes
Grantee:Fabio Daumas Nunes
Home Institution: Faculdade de Odontologia (FO). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Flávia Caló de Aquino Xavier

Abstract

The homeobox gene functions in regulating morphogenesis and embryo differentiation, admitting the possibility of its abnormal expression to participate in the progression of tumors. Preliminary studies in our laboratory verified the participation of some homeobox genes in oral squamous cell carcinoma, when attempting to find markers of aggressiveness. The genes HOXD10, HOXD11, IRX4, ZHX1 and PROX1 showed differences in the expression of mRNA in the tumor in relation to its margin, and in more aggressive and less aggressive tumors depending on the gene, which may be associated with the function of oncogenes for some, or the silencing of tumor suppressor function for others. Thus, given that changes associated with carcinogenesis share events of genomic amplification and silencing of tumor suppressor genes by methylation, this work aims to extend the study of above-mentioned homeobox genes through epigenetic and genetic analysis in oral squamous cell carcinoma, in order to correlate to correlate this information with the findings of transcripts and protein expression, as well as with the clinical behavior of the tumor, still seeking functional answers for genes that may be involved in these processes. Other homeobox genes as HOXA5, HOXA7, HOXA9, HOXB5, HOXB13, HOXC12, known to be involved in epigenetic events, will also be included, besides the HOXC13, whose low expression levels between the samples of tumors and margins motivates its study. The correlation with the expression of DNMTs genes, that encode enzymes responsible for DNA methylation, will bring new information regarding the involvement of them in oral cancer, and possible interaction with epigenetic events of homeobox genes. (AU)

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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)
SETUBAL DESTRO RODRIGUES, MARIA FERNANDA; ESTEVES, CARINA MAGALHAES; AQUINO XAVIER, FLAVIA CALO; NUNES, FABIO DAUMAS. Methylation status of homeobox genes in common human cancers. Genomics, v. 108, n. 5-6, p. 185-193, . (08/06223-3, 10/08720-4)
AQUINO XAVIER, FLAVIA CALO; DE SOUZA SETUBAL DESTRO, MARIA FERNANDA; ESTEVES DUARTE, CARINA MAGALHAES; NUNES, FABIO DAUMAS. Epigenetic repression of HOXB cluster in oral cancer cell lines. ARCHIVES OF ORAL BIOLOGY, v. 59, n. 8, p. 783-789, . (09/06521-7, 10/08720-4)

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