Changing Patterns of Gene Expression Identify Multiple Steps During Regression of Rat Prostate in Vivo

Abstract

The rat ventral prostate is an androgen-dependent organ that undergoes dramatic cell death upon removal of testosterone by surgical castration. Several well characterized criteria, such as nuclear condensation, organelle blebbing, and DNA fragmentation, have been used to demonstrate that most of this cell loss is due to programmed cell death, or apoptosis, of the secretory epithelial cells. In addition to changes in morphology, it is well known that cells undergoing apoptosis show alterations in gene expression, and it is widely assumed that many of these genes are directly involved in the mechanism of programmed cell death. Using poly A ϩ RNA derived from normal rat prostate as well as from the regressing prostates of castrated rats, we have used a PCR-based subtractive hybridization approach to generate complementary DNA (cDNA) libraries greatly enriched in cDNAs strongly regulated during rat prostate regression. Several hundred of the genes represented in these libraries appear to be strongly regulated during prostate regression and most of these are prostate specific. Sequence analysis indicates that up to 30% of these clones are similar or identical to genes of known function, approximately 20% are similar to expressed sequence tags (ESTs), and as many as 50% of these clones have not been characterized previously. Analysis of selected clones using in situ hybridization indicates that they are expressed specifically in prostate epithelial cells, and that certain of these clones are regulated temporally in a pattern consistent with apoptosis. The patterns of gene expression include: 1) genes whose expression decreases uniformly after removal of androgen, indicative of androgen sensitive genes; 2) genes whose expression increases in apoptotic prostate cells and in other tissues, suggesting a class of genes generally involved in apoptosis; 3) and genes whose expression increases in individual regressing prostate epithelial cells, suggesting a class of prostate specific genes associated with apoptosis.

Genes upregulated during castration‐induced rat prostatic apoptosis: cloning and characterization of new cDNAs

“…Furthermore, L7 can block the cell cycle in G1 and induce apoptosis in Jurkat T‐lymphoma cells [30]. On the other hand, we and others have previously shown ribosomal proteins L5 and S27 to be upregulated in the same model [31,32]. Hence, although apoptosis is known to be characterized by decreased overall protein synthesis, it is possible that the need to rapidly synthesize several apoptosis‐specific proteins might necessitate increased ribosome production.…”

Computational methods for theidentification of differential and coordinated gene expression

“…Numerous recent review articles have commented on the enormous potential of microarray-based transcriptome studies (see, for example, refs [37][38][39][40][41][42]. However, tag-counting methods are still very popular and important results have been obtained with the EST (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) or SAGE (54)(55)(56)(57)(58)(59) protocols.…”

A Multiscale, Mechanism-Driven, Dynamic Model for the Effects of 5α-Reductase Inhibition on Prostate Maintenance

“…Testosterone (T) is metabolized by 5aR into the more potent 5α-dihydrotestosterone (DHT) [6], [7], the driving force of prostate gene-regulation [8], [9], [10], [11], [12], [13], [14]. In turn, DHT controls the gene expression of 5aR, creating a feedback control loop [15].…”