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Genes related with proliferation or differentiation of keratinocytes: evaluation of expression in head and neck squamous cell carcinomas and its role on neoplastic phenotype

Grant number: 08/06359-2
Support type:Regular Research Grants
Duration: February 01, 2009 - January 31, 2011
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Eloiza Helena Tajara da Silva
Grantee:Eloiza Helena Tajara da Silva
Home Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

The epithelium protects the underlying tissues from environmental influences such as physical and chemical damages, loss of water, microorganisms infections and body heat loss. The most superficial layer of keratinizing (cornified) stratified squamous epithelia, such as epidermis, hard palate and gingival tissue is formed by deceased cells which lack nuclei and cytoplasmic organelles. These cornified (dead) cells are reduced to squames, filled with keratin protein and surrounded with a cornified envelope composed of crosslinked proteins and lipids, such as small proline-rich proteins (SPRRs). In a previous study of our group, using SAGE libraries of squamous cell carcinomas of head and neck (CECP) and matched normal tissues, differentially expressed transcripts were identified, such as keratin 6A(KRT6A), keratin 19 (KRT19), small proline-rich proteins (SPRR2F, SPRR2E and SPRR3) and kallikrein 8 (KLK8), the latter already described in literature as involved in keratinocytes proliferation and skin desquamation. The present project aims (a) to evaluate the expression profile of KRT6A, KRT19, SPRRs and KLK8 genes in cell lines and primary tumors from head and neck, as well as in normal keratinocytes lines; (b) depending on the expression profile of these transcripts in the cell lines, to block or to induce the expression of the corresponding genes for evaluation of its effect on neoplastic phenotype and (c) to characterize the expression profile of microRNAs in cell lines and primary tumors from head and neck, as well as in normal keratinocytes lines. The results may contribute for a better understanding of the role of these genes in healthy and disease, as well as the characterization of molecular pathways involved in the development of the CECPs. (AU)