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Interface between aberrant glicosylation of tumors and the unfolded protein response: target for chemosensitization in melanomas?

Grant number: 08/02164-2
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2008
Effective date (End): June 30, 2010
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Roger Chammas
Grantee:Luciana Maria Dorneles de Oliveira
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:98/14247-6 - Center for Research on Cell-Based Therapy, AP.CEPID

Abstract

The resistance of cancerous cells to the chemotherapeutic antineoplastics known is a big problem in treatment of melanoma, being the cisplatin one of the most utilized in this treatment. The glycoproteins of tumour cells present structural modifications in its standards of glycosylation, being many of them common and have been associated with the trials of tumor metastasis, invasion and progression. In the endoplasmatic reticulum(ER), during the protein synthesis, begins the formation of the N-glycosylation that in its initial form permits the recognition by molecules involved in the protein folding quality control. An accumulation of unfolded proteins in the ER generates a stress in this organelle being able to provoke a trial cytoprotective named unfolded protein response (UPR), that when activated constantly can trigger apoptosis. This project is going to study the relation between aberrant N-glycosylation and the resistance of tumors through the evaluation of the effects of the blockade of the protein folding quality control of the ER, associating it with induction of ER stress and with apoptosis. Being like this will submit itself cells of the lineages melan-a, TM1 and TM5 to four kinds of treatment: combination of cisplatina and castanospermina (this block the recognition by the protein folding quality control), only cisplatina, only castanospermina and those that will not have addition of chemoterapics; and will compare the protein expression and transcription of molecules involved in the N-glycosylation, in the ER stress and with apoptosis.