Transcription regulators are transiently expressed during the prostate gland adaptation to the hypoandrogenic environment
Umar Nishan1, Rafaela Rosa-Ribeiro1, Carlos Lenz Cesar2,3 and Hernandes F. Carvalho1,3
1Department of Structural and Functional Biology, Institute of Biology, 2Department of Quantum Electronics, Institute of Physics Gleb Wataghin, State University of Campinas (UNICAMP) and 3INFABiC – National Institute of Science and Technology in Photonics Applied to Cell Biology, Campinas SP, Brazil
Offprint requests to: Hernandes F. Carvalho, Institute of Biology, Unicamp, Rua Charles Darwin, sn, Bloco N, Salas 10/11, 13083-863 Campinas SP, Brazil. e-mail hern@unicamp.br
Summary. The high incidence of prostatic diseases, including malignant tumors, makes the understanding of prostate biology very important. Androgen deprivation, blockade by orchiectomy, or chemical castration causes prostate and tumor shrinkage. The gene networks involved in a cell type-specific fashion are rather unknown. This work was undertaken to identify genes with annotated function in transcription regulation that might define transitions in gene expression. A total of 15 potential regulatory genes were identified. Validation by qRT-PCR showed that Zfp703 and Arid1a exhibit expression maxima at day 1; Ash2l, Nelf, Pbx3, Eya2 at day 4; Dmrt2 at day 5 and Lbh and Sox1 at day 7 after castration. Using immunohistochemistry, we further determined that PBX3 was found in both stromal and epithelial cells, whereas ARID1A and NELF were restricted to the epithelium, and DMRT2 and EYA2 were exclusively found in the stroma. Though the proteins ZFP703 and ASH2l were not found in any experimental condition, their mRNAs were located by in situ hybridization in both epithelium and stroma. In conclusion, androgen deprivation triggers the expression of temporally regulated gene sets in both epithelial and stromal cells. These gene subsets will help establish the regulatory gene expression programs orchestrating the castration-induced remodeling of the prostate gland, and represent putative targets to increase the efficacy of androgen-deprivation to induce epithelial (and cancer) cell death. Histol Histopathol 34, 1025-1036 (2019)
Key words: Castration, Prostate, Stroma, Transcription factors, Tissue remodeling
DOI: 10.14670/HH-18-105