title: Differential gene regulation during programmed death (apoptosis) versus proliferation of prostatic glandular cells induced by androgen manipulation.
abstract: By manipulating the circulating blood level of androgen, it is possible to induce either the programmed death (apoptosis) or proliferation of prostatic glandular cells. To examine the role of differential gene regulation in these two procedure, the expression of the mRNA of a series of genes was quantitated on a per cell basis during the androgen ablation-induced programmed death of rat prostatic glandular cells. These results were then compared to quantitative analysis of the mRNA expression of these same series of genes during the proliferative regrowth of prostatic glandular cells induced in rats castrated for 1 week before being treated with exogenous androgen replacement. These comparisons demonstrated that androgen ablation-induced programmed death of prostatic glandular cells share several (i.e. c-myc, H-ras, and tissue transglutaminase), but not most, of the epigenetic changes associated with androgen-stimulated proliferation of these cells. No enhancement of the mRNA expression of several genes required for entrance of prostatic glandular cells into the S-phase of the proliferative cycle (i.e. histone-H4, c-fos, p53, and ornithine decarboxylase) occurred during androgen ablation-induced programmed death of these cells. These results demonstrated that neither entrance into the S-phase nor progression through a defective proliferative cell cycle is involved in androgen ablation-induced programmed death of prostatic glandular cells. This was further supported by the observation that there is a set of genes (i.e. TRPM-2, transforming growth factor-beta 1, alpha-prothymosin, and calmodulin) in which mRNA expression is only enhanced during programmed cell death and not during proliferation of prostatic glandular cells induced by androgen replacement. These results demonstrate that prostatic programmed cell death is a distinct pathway from cell proliferation involving differential gene regulation.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, Maryland.
authors.forename: Y
authors.initials: Y
authors.lastname: Furuya
authors.forename: J T
authors.initials: JT
authors.lastname: Isaacs
mesh_terms: D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000166:cytology* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000728:Androgens; D002147:Calmodulin; D012333:RNA, Messenger