Prostatic Diseases in the Elderly Men: Glandular Microenvironment Signaling of IGFR-1, Steroid Hormone Receptors, Matrix Metalloproteinases and Dystroglycans.
Amanda Hetzl, Wagner Favaro, Fabio Montico, Ubirajara Ferreira, Athanase Billis, Valeria Cagnon. UNICAMP/Institute of Biology, Campinas, Sao Paulo, Brazil; UNESP, Campinas, Sao Paulo, Brazil; UNICAMP, Campinas, Sao Paulo, Brazil
Background: Senescence is a determining factor for the occurrence of morphological changes in the prostate. Thus, the objective of this work was to characterize and correlate the α and β-dystroglycans (αDG, βDG), androgen receptor (AR), α and β-estrogen receptors (αER, βER), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and insulin-like growth factor receptor (IGFR-1) reactivities in both stromal and epithelial compartments of elderly men without prostatic lesion and with Benign Prostatic Hyperplasia (BPH), High Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Prostatic Cancer (PC).
Design: Sixty samples from the prostatic peripheral zone of autopsies and/or radical prostatectomies of 60-90 year old patients were divided into standard (no lesions), HGPIN, PC and BPH groups and analyzed by means of immunohistochemistry and Western Blotting analyses.
Results: The results showed increased IGFR-1, MMP-2 and MMP-9 protein levels in the PC and HGPIN groups in relation to other groups. Decreased αDG and βDG protein levels were verified in the PC and HGPIN groups in relation to the BPH and standard groups. Intensified AR immunoreactivity was verified in the epithelial compartment in all studied groups. αER immunoreactivity was more intense in the epithelial compartment in the PC and HGPIN groups than in the other groups. βER immunoreactivity was weaker in the epithelial compartment of the HGPIN and PC groups than in the BPH and standard groups.
Conclusions: Abnormal αDG, βDG, IGFR-1, MMP-2 and MMP-9 protein levels certainly compromised the glandular epithelial-stromal interaction in the senescence. The differential steroid hormone receptor reactivities in the glandular lesions in both prostatic compartments indicated different paracrine signals to the dynamics of the prostate and pointed out the importance of estrogenic pathways in the activation of these changes. Also, these findings indicated that there was a direct association between IGFR-1, MMPs and steroid hormone receptors, pointing towards IGFR-1 as a target molecule in prostate therapy and a possible factor for MMPs positive signaling.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 140, Monday Afternoon