RHBDD2 gene expression profile in low and high-grade brain tumors reveals its upregulation in the malignant subtypes

FERRETTI V.; FACCHINETTI M.M.; CURINO A. C.; PALMA S.; LACUNZA E.; ABBA M.C.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias. LXII Reunión Anual de la Sociedad Argentina de Investigaciones Clínicas (SAIC); 2017

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