RHBDD2 GENE EXPRESSION PROFILE IN LOW AND HIGH-GRADE BRAIN TUMORS REVEALS ITS UPREGULATION IN THE MALIGNANT SUBTYPES.

FERRETTI V; PALMA S; FACCHINETTI, MM; CURINO AC; ABBA MC; LACUNZA E

La Plata

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Abstract: The Rhomboid family is a heterogeneous group of membraneproteins involved in various functions such as cell signaling,development, apoptosis or stress response to endoplasmic reticulum(ER). Several members have been associated to neurodegenerativediseases and cancer. In previous studies, we determinedthat the expression of the gene RHBDD2, a member of the family, isincreased in the advanced stages of breast and colorectal cancersand it is induced by the chemotherapeutic agent 5-fluorouracil (5-Fu)in colon cancer cells. We also showed that RHBDD2 is associatedto the ER stress pathway known as the unfolded protein response(UPR). In this sense, UPR is highly active in glioma tumors andits induction drives chemoresistance in glioma cells. We hypothesizedthat the overexpression of RHBDD2 in the advanced stagesof cancer and its induction against 5-Fu provides the tumor cellswith a stress-resistant phenotype. In an exploratory study, usinghuman brain tumor samples, cell lines, gene expression databasesand bioinformatic analysis we determined the expression profileof RHBDD2 and UPR genes in different subtypes of brain tumors(Oligodendrogliomas, Astrocitomas and Glioblastomas). Using IHC,RTPCR and phenotypic assays we observed that RHBDD2 expressionvaried across the different types of tumors, being higher in glioblastomas(p