INVESTIGADORES
CURINO Alejandro Carlos
congresos y reuniones científicas
Título:
RHBDD2 gene expression profile in low and high-grade brain tumors reveals its upregulation in the malignant subtypes
Autor/es:
FERRETTI V.; PALMA S.; FACCHINETTI M.M.; CURINO A. C.; ABBA M.C.; LACUNZA E.
Lugar:
Bs. As.
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias. LXII Reunión Anual de la Sociedad Argentina de Investigaciones Clínicas (SAIC); 2017
Institución organizadora:
Sociedad Argentina de Investigaciones Clínicas (SAIC)
Resumen:
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<0.01). We also evidenced that silencing of RHBDD2 expression in the cell line SHS5Y, widely used as a cell model of DAergic neurons, contributed with a decrease in cell migration and proliferation (wound healing assay, p<0.05) and also affected the expression of UPR related genes. Survival analysis in TCGA datasets indicated a significant association (p<0.01) between high RHBDD2 expression and short-term survival factors such as grade, age and tumor localization. Although more studies are being carried out, the perspectives of these results position RHBDD2 as an interesting target to be considered for malignant glioma therapeutics.