Increased expression and activity of p75NTR are crucial events in azacitidine-induced cell death in prostate cancer.

Abstract:

:The high affinity nerve growth factor (NGF) NGF receptor, p75NTR, is a member of the tumor necrosis factor (TNF) receptor superfamily that shares a conserved intracellular death domain capable of inducing apoptosis and suppressing growth in prostate epithelial cells. Expression of this receptor is lost as prostate cancer progresses and is minimal in established prostate cancer cell lines. We aimed to verify the role of p75NTR in the azacitidine-mediated antitumor effects on 22Rv1 and PC3 androgen-independent prostate cancer cells. In the present study, we reported that the antiproliferative and pro-apoptotic effects of 5-azacytidine (azacitidine) were more marked in the presence of physiological concentrations of NGF and were reduced when a blocking p75NTR antibody or the selective p75NTR inhibitor, Ro 08-2750, were used. Azacitidine increased the expression of p75NTR without interfering with the expression of the low affinity NGF receptor TrkA and induced caspase 9-dependent caspase 3 activity. Taken together, our results suggest that the NGF network could be a candidate for future pharmacological manipulation in aggressive prostate cancer.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Gravina GL,Marampon F,Sanità P,Mancini A,Colapietro A,Scarsella L,Jitariuc A,Biordi L,Ficorella C,Festuccia C

doi

10.3892/or.2016.4832

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

125-30

issue

1

eissn

1021-335X

issn

1791-2431

journal_volume

36

pub_type

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