TEMOZOLOMIDE MODULATES WNT/BETA CATENIN SIGNALING IN PROLACTINOMA CELLS

DEMARCHI G; VALLA S; BONADEO N; VITALE DAIANA; ALANIZ L; BERNER SILVIA; CRISTINA C

Mar del Plata

Congreso; Reunion Anual SAIC-SAI-SAFE-NANOMEDAR-AACYTAL; 2016

SAIC, SAI - SAFE

Some of them become refractory to conventional therapies turninginto aggressive tumors. Wnt signaling plays a role in cellrenewal, tumorigenesis and chemoresistance. Previous resultsof our group demonstrate expression of βCATENIN in a cohort ofhuman pituitary adenomas including prolactinomas and activationof the Wnt pathway in experimental lactotroph hyperplasia. Theuse of the alkylating agent Temozolomide to treat aggressiveprolactinomas is recent with successful results in some cases.Here we aimed to study the activation state of Wnt pathway inbasal conditions and under Temozolomide treatment in the MMQprolactinoma cell line. Cells were treated with Wnt3a ligand (1ng/ml) and/or Temozolomide (200uM) along 48 hs. Cell proliferationwas evaluated by MTT and mRNA and protein levels by real timePCR and Western Blot respectively. Basal expression of Frizzledreceptors, Lrp correceptor and βCATENIN, CYCLIND1 and CMYCcomponents were determined. We observed an increasedcell proliferation under Wnt3a treatment indicating a possiblerole of Wnt pathway in the development of these tumors. In ourexperimental model Temozolomide decreased cell proliferationand Prolactin and Vegf synthesis. The angiogenic capabilityof Temozolomide treated or untreated cells was evaluated ina scratch assay with endothelial cells which showed reducedmigration compared to controls. Temozolomide reduced mRNAexpression of the Wnt pathway components βcatenin, the targetgene CyclinD1, and the activated βCATENIN (p