Temozolomide modulates Wnt/BCatenin signaling in prolactinoma cells

DEMARCHI, GIANINA; VALLA, SOFÍA; BONADEO, NADIA; VITALE, DAIANA; ALANIZ, LAURA; BERNER, SILVIA; CRISTINA, CAROLINA

Mar del Plata

Congreso; Reunión Anual Conjunta SAIC-SAI-SAFE; 2016

SAIC-SAI-SAFE

Prolactinomas are the most frequent pituitary adenomas. Some of them become refractory to conventional therapies turning into aggressive tumors. Wnt signaling plays a role in cell renewal, tumorigenesis and chemoresistance. Previous results of our group demonstrate expression of βCATENIN in a cohort of human pituitary adenomas including prolactinomas and activation of the Wnt pathway in experimental lactotroph hyperplasia. The use of the alkylating agent Temozolomide to treat aggressive prolactinomas is recent with successful results in some cases. Here we aimed to study the activation state of Wnt pathway in basal conditions and under Temozolomide treatment in the MMQ prolactinoma cell line. Cells were treated with Wnt3a ligand (1ng/ml) and/or Temozolomide (200uM) along 48hs. Cell proliferation was evaluated by MTT, and mRNA and protein levels by real time PCR and Western Blot respectively. Basal expression of Frizzled receptors, Lrp correceptor and βCATENIN, CYCLIND1 and C-MYC components were determined. We observed an increased cell proliferation under Wnt3a treatment indicating a possible role of Wnt pathway in the development of these tumors. In our experimental model Temozolomide decreased cell proliferation and Prolactin and Vegf synthesis. The angiogenic capability of Temozolomide treated or untreated cells was evaluated in a scratch assay with endothelial cells which showed reduced migration compared to controls. Temozolomide reduced mRNA expression of the Wnt pathway components βcatenin, the target gene CyclinD1, and the activated βCATENIN (p