INVESTIGADORES
ALANIZ Laura Daniela
congresos y reuniones científicas
Título:
Wnt/β-Catenin Activation in Prolactinomas. Relevance in New Treatments for Aggressive Cases
Autor/es:
GIANINA DEMARCHI; SOFIA VALLA; DAIANA VITALE; FIORELLA SPINELLI; LAURA ALANIZ; BERNER, SILVIA; CAROLINA CRISTINA
Lugar:
Orlando
Reunión:
Congreso; ENDOCRINE MEETING 2017; 2017
Institución organizadora:
Endocrine Society
Resumen:
Despite the increasing efforts to deeply understand the reasons of tumor development, there are some mechanisms that still remain unclear. The Wnt pathway promotes cell self-renewal and differentiation. The Wnt signaling ligands stabilize β-Catenin allowing its nuclear translocation and target gene transcription. Is it well known that dysregulation of Wnt pathway as well as β-Catenin nuclear localization lead to the development of a vast type of tumors, but their role in pituitary adenomas remains unclear.Here we hypothesize that the canonical Wnt pathway is active and involved in pituitary tumor development and maintenance. Then we aimed to assess the expression and localization of β-Catenin in a cohort of human pituitary adenomas and to study the effect of Wnt signaling activation on tumor lactotrope cell function in vitro.β-Catenin expression and localization were assessed by immunohistochemistry. The MMQ tumor lactotrope cells were cultured in complete DMEM:F12 medium and treated with Wnt3a ligand (1ng/ml) and/or Temozolomide (200uM). The mRNA and protein levels were determined by RT-qPCR and Western Blot respectively. VEGF secretion was quantified by ELISA, and cells in synthesis stage (S phase) of the cell cycle or in apoptosis were determined by flow citometry. Cell proliferation was determined by MTT assay.We detected β-Catenin staining in all of the cases studied and found different distribution pattern between the different subtypes of pituitary adenomas. Interestingly, within them, prolactinomas had the highest nuclear/cytoplasm and nuclear/membrane β-Catenin ratio, highlighting the role of Wnt pathway activation in this pituitary tumor subtype.We also found Wnt pathway activation in the MMQ tumor lactotrope cells through the increment in the active β-Catenin expression (p