Forkhead box factors (FOX) modulate Glucocorticoid and Androgen receptors activity in prostate cancer

BRANDANI, JAVIER; LEONARDI, DAIANA; ABBATE, MERCEDES; VAZQUEZ, ELBA; COTIGNOLA, JAVIER

Mar del Plata

Congreso; LXI Reunion Anual de la Sociedad Argentina de Investigacion Clinica; 2016

Sociedad Argentina de Investigacion Clinica

Deregulation of hormonal receptors expression is responsible for the development and progression of prostate cancer (PCa). The Androgen receptor (AR) is involved in the PCa progression. The glucocorticoid receptor (GR) might also have oncogenic and/or tumor suppressor activities depending on the presence/absence of AR and other cofactors such as the forkhead box (FOX) family. We previously showed that the expression of FOXA1, FOXM1, FOXO1 and FOXO3 could be modulated by testosterone and dexamethasone (dex); conditions that simulate different stages of progression and treatment of PCa. We aim to deepen in the knowledge of these mechanisms using PC3 (AR-, GR+) and C4-2B (AR+,GR+) PCa cell lines as in vitro models. Cells were transfected with FOXA1 or FOXM1 shRNAs to knockdown gene expression. Diminished cell proliferation and altered cellular morphology were observed in FOX-knockdown cells. PC3 cells were also transfected with a constitutive active AR which was found to modulate FOXs expression. To study the transcriptional activity of GR, cells were transfected with a reporter plasmid containing 3 glucocorticoid response elements. Dex treatment resulted in an increment in luciferase levels (p