Regressão prostática pós-castração

Abstract

Prostate development, physiology and cancer depend on a fine balance between the levels of androgens and estrogens acting via the androgen receptor (AR) and the estrogen receptors (ER e ER), respectively. It is known that the kinetics of apoptosis are different in the rat ventral prostate (VP) of castrated rats (Cas group) and in rats subjected to 17-estradiol high dose (group E2) or their combination (group Cas+E2), with an evident additive effect in the latter situation . In this work, we investigated elements in common and exclusive to each of these hormonal conditions, employing morphological analysis, components of the AKT/PTEN pathway and analyses of differential gene expression using DNA microarrays combined with a search for transcription factors (TF). The VP weight was significantly reduced in the Cas and Cas+E2 groups. In the E2 group, the remarkable effects were the presence of protein aggregates in the cytoplasm, and cell proliferation and layering of the epithelium. Another important aspect was the detachment of the smooth muscle cells from the epithelium when it showed infolds. In the Cas+E2 group, the different aspects observed in the individual groups were observed, except by less frequent epithelial layering. The biochemical analysis showed a significant reduction in 4EBP phosphorylation in the groups E2 and Cas+E2 (similar tendency was observed in the Cas group). There is a large number of differentially expressed genes as compared to the controls and shared by the different treatments, Surprisingly, there was no reduction in the expression of the probasin gene in the E2 group. The recovered gene onthologies and enrichment terms revealed the absence of enrichment terms among the genes exclusive to the Cas+E2 group, what conciliates with the Idea that the observed changes in this group are identical or at least very similar to those occurring in the individual treatments. In conclusion, the search for TF binding sites in the promoter region of the regulated genes and the identification of TF in the regulatory pathways obtained for the enrichement terms indicated the TF Evi-1, NF-Y, HNF-4, Elk-1, GATA-2, c-Rel, v-Myb and NFB as candidates to regulate the events associated with prostate regression. LISTA DE ABREVIATURAS 4EBP: do inglês, Eukaryotic translation initiation factor 4E-1A-binding protein4EBP2: do inglês, Eukaryotic translation initiation factor 4E-binding protein 2 AKT: do inglês, serine/threonine protein kinase Akt AR: receptor de andrógeno (sigla do inglês, androgen receptor) ARE: elemento responsivo a androgénos (do inglês, androgen responsive element) BCL2: do inglês, B-cell CLL/lymphoma 2 CAB: bloqueio combinado dos andrógenos (do inglês, combined androgen blockade) Cas: grupo castrado por 72 horas Cas: grupos de animais castrados Cas+E2: grupo de animais castrados e que receberam alta dose de estrógeno por 72 horas CD44: gliproteína de superfície cellular CD44 Ck: citoqueratina CML: célula muscular lisa DHT: dihidrotestosterona (5-dihidrotestosterona ou 5-androstan-17-ol-3-o...