THE EPIGENETIC EZH2/H3K27me3 AXIS MODULATES LACTOTROPH TUMOUR CELL PROLIFERATION

ZLOCOWSKI N; SOSA L DEL V.; GUIDO, C; MUKDSI, J. H.; TORRES, A I; PETITI J P

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2022

Pituitary Neuroendocrine tumours (PitNETs) genes could be inactivated via epigenetic modifications, suggesting an important role of epigenetic regulatory factors in PitNET tumorigenesis. However, the inhibition of these factors in order to propose new therapeutic strategies remain poorly understood. The objective of the present study was to examine the participation of the EZH2/H3K27me3 axis in the proliferation of lactotroph tumour cells. The experimental prolactin (PRL) tumour model in adult Fisher rats and the pituitary tumoral PRL-secreting cell GH3 were used. EZH2 and H3K27me3 expression was analysed by Western Blot and Immunohistochemistry. The H3K27me3/PRL co-expression was performed by immunofluorescence and immunoelectron labelling. mRNA levels of p21, p53, Cdk4 and Cyclin D1 were determined by qPCR. GH3 cell line was treated with specific EZH2 inhibitor GSK343 (5-10uM) for 72h and then MTT assay and BrdU uptake were carried out. Statistic: ANOVA-Tukey or t-test. EZH2 and H3K27me3 expression increased with a higher number of positive nuclear marks, in experimental PRL tumours respect to control pituitaries. In addition, H3K27me3/PRL co-expression increased in tumoral glands respect to normal glands (p