Synergic effects of TGF-b and Octreotide on pituitary tumor cell proliferation

PICECH, F; SOSA L DEL V.; PEREZ P; GUTIÉRREZ, S; DE PAUL AL; TORRES, A I; PETITI J P

Praga

Congreso; 12 th International Congress of Cell Biology; 2016

The precise response to enviroment signals is essential for the cell funtion, development and survival, therefore an alteration in the receptors responsible of transmitting those signals to inside of cells is closely associated whit tumor progression and resistence to treatments. Pituitary adenomas exibit a low expression of inhibitory receptros, as those for somatostatin (SSTR) and TGF-B1(TGF-bR), which has been associated with the resistence that these tumors display against conventional terapy.Our main objetive was to elucidate a possible crosstalk between both inhibitory pathway in pituitary adenoma cells, Gha3 rat pituitary tumor cells were treated for 24 hours with SSTR and TGF-BR agonist, octreotide (OCT, 10 and 100 nM) and TGF-b1 (4mg/ml) respectively. SSTRs and TGF-bRs mRNA expression was analysed by PCR, hormone secretion (PRL) by RIA, and cell proliferation and cycle progression by flow cytometry. In addition, the influece of the agonists on cell ultra-structure and morphology was examined by electron microscopy.The co-incubation of OCT with TGF-b1 induced an increase of SSTR and TGF-b1R mRNA expression and a decrease of the proliferation marker Ki67 and PRL secretion compared to treatments alone. Futhermore, OCT dimished the expression of cell cycle regulators Cdk4 and Ciclin D1, ana incremented the percentage of cell in S and G2/M phase. Nevertheless, none of the treatments induced changes in cell morphology.To summarize, these results prove that the treatment of OCT in presence of TGF-b1 modifies SSTRs and TbRs expression leading to an inhibition in cell proliferation ans hormone secretion, which suggests a possible interaction between both anti-mitogenic siganls in GH3 cells. Moreover, OCT exerts and anti-proliferative effect by decreasing the expression of proteins that control the cell cycle and possibly inducing cell cycle arrest in proliferative phases. Such results highlight the importance of comprehending the connecion amog defferent ant-mitogenic signalling pathways and how they can be modulated to obtain a better cell response on the context of tumoral resistence to treatments.