Nerve growth factor signaling in prostate health and disease.
The prostate is one of the most abundant sources of nerve growth factor (NGF) in different species, including humans. NGF and its receptors are implicated in the control of prostate cell proliferation and apoptosis and it can either support or suppress cell growth. The co-expression of both NGF receptors, p75(NGFR) and tropomyosin-related kinase A (trkA), represents a crucial condition for the antiproliferative effect of NGF; indeed, p75(NGFR) is progressively lost during prostate tumorigenesis and its disappearance represents a malignancy marker of prostate adenocarcinoma (PCa). Interestingly, a dysregulation of NGF signal transduction was found in a number of human tumors. This review summarizes the current knowledge on the role of NGF and its receptors in prostate and in PCa. Conclusions bring to the hypothesis that the NGF network could be a candidate for future pharmacological manipulation in the PCa therapy: in particular the re-expression of p75(NTR) and/or the negative modulation of trkA could represent a target to induce apoptosis and to reduce proliferation and invasiveness of PCa.
Arrighi
Nicola
N
Division of Urology, University of Brescia Medical School, P.le Spedali Civili 1, 25124 Brescia, Italy.
Bodei
Serena
S
Zani
Danilo
D
Simeone
Claudio
C
Cunico
Sergio Cosciani
SC
Missale
Cristina
C
Spano
Pierfranco
P
Sigala
Sandra
S
D000230:Adenocarcinoma / Q000378:metabolism*; D006801:Humans; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D014947:Wounds and Injuries / Q000378:metabolism
D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA