Expression of p190A during apoptosis in the regressing rat ventral prostate.

Abstract

After hormonal ablation, 90% of the secretory epithelial cells of the prostate undergo apoptosis, and the remaining cells are reorganized as the tissue is remodeled. Using differential display RT-PCR of total RNA extracted from the rat ventral prostate before and 4 days after castration, we have cloned and sequenced a number of complementary DNAs whose cognate messenger RNAs (mRNAs) may be either up- or down-regulated during prostatic regression. One sequence of particular interest, 25.2, is up-regulated after castration and is homologous to p190, a protein associated with cytoskeletal reorganization. RT-PCR has confirmed that the steady state level of p190A mRNA is increased in the rat ventral prostate after castration, and Western blot analysis indicates that the protein levels for p190A also increase. The steady state level of p190B mRNA, the second isoform of p190, does not appear to change significantly after hormone ablation. Immunohistochemical analysis demonstrates that p190A is up-regulated primarily in the columnar epithelial cells that actively undergo cell death after hormone ablation. As Rho-GAP signaling had been shown to be influenced by p190 levels, leading to the disassembly of focal adhesion contacts and the loss of cytoskeletal architecture, we also measured the changes in Rho-GAP during prostate regression. Rho-GAP levels do not change significantly, suggesting that changes in stoichiometry of the interaction between p190A and Rho-GAP may be a prerequisite for the initiation of cytoplasmic condensation. These intracellular events coupled with the proteolytic degradation of the extracellular matrix appear to be integral to the apoptotic process in glandular epithelia.