Intranuclear distribution of androgen receptors in human prostate carcinoma

Abstract

Androgen receptors in nuclei from human prostate carcinomas were characterized on the basis of their solubilization by, or resistance to, micrococcal nuclease. By this means, androgen receptors were assigned to three nuclear categories: those associated with nuclease-resistant structures, those associated with chromatin and those apparently uncommitted by association with either of these. Prostate carcinoma nuclei contained high concentrations (57-82% of total nuclear content) of nuclease-resistant androgen receptors. This was a different pattern from that observed previously for benign hypertrophic prostate epithelial nuclei which contained a variable high proportion of uncommitted androgen receptors. The differences could not be attributed to differential losses to cytosol, or to loss of functionality, as determined in vitro. The differences in distribution could reflect different responses of diseased cells to androgens, or the intervention of other factors more relevant to the disease process.

Binding of epidermal growth factor by human normal, hypertrophic, and carcinomatous prostate

“…Infrequently, BPH tissue was obtained after retropubic prostatectomy, and on these occasions tissues classified as histologically normal (HN) were derived from peripheral areas of these samples. These tissues were chopped into approximate 3 mm3 pieces [23], which were checked histologically to confirm assessment on whole tissues.…”

Intranuclear Androgen Receptor Deployment and Protooncogene Expression in Human Diseased Prostate

“…1). Cancer cells containing a high proportion of nuclease-resistant receptors can exist in a varying environment of receptor-negative cancer cells and/or normal cells (in which the distribution of extractable to resistant receptors is 1:1 [8,14]), which would affect the resistant receptor to total receptor ratio in dif ferent ways. Fig.…”

“…Smaller fragments damaged by TUR were discarded and only those from which charred material could be removed to leave satisfacto rily uninjured samples were used [15]. Homogenization of tissue, preparation of nuclei and exhaustive nucleolysis to yield total pop ulations of nuclease-extractable and nuclease-resistant androgen re ceptors have been described [13,14], Under the conditions em ployed, 'nuclease-resistant' described those receptors which had not been solubilized during a digestion procedure following which no more nuclear material could be released by the action of micrococ cal nuclease (used routinely) or any other nuclease alone. In this report, 'nuclease-extractable' describes those androgen receptors which have been solubilized during such a procedure.…”

“…However, this new emphasis presents fresh complications. Determina tions on high-ionic-strength extracts of nuclei [1][2][3][4][5] ig nore a considerable population of androgen receptors which is resistant to such treatment [2][3][4]8], and which has, by virtue of its association with the nuclear matrix, been proposed as a biologically active component [2], In both cancer and benign prostate hypertrophy (BPH), nuclear androgen receptors may differ quantitatively or in intranuclear deployment from the normal condition [8,[10][11][12], Moreover, the intranuclear deployment of androgen receptors can differ markedly between cancer and BPH samples of similar quantitative receptor con tent [13,14], Anomalies in androgen receptor distribu tion may relate not only to the aetiology of the diseases but also to the disparate development of carcinoma and BPH. This report describes in greater detail the dissimi larities in intranuclear deployment of androgen recep tors in prostate cancer and BPH, and also recounts pre liminary investigations into the relationships of andro gen receptors and the expression of genes which may be implicated in the initiation or progression of cancer.…”

APRIN is a unique Pds5 paralog with features of a chromatin regulator in hormonal differentiation

“…The long-term, differentiation-related hormonal changes, however, argue against the participation of plasma membrane-based mechanisms because molecules involved in these pathways reach a peak in a few minutes and their effects last only for a couple of hours [13]. Chromatin involvement, on the other hand, was confirmed by receptor localization studies [14,15], receptor interaction assays [16] and by detection of global rearrangements of the chromatin architecture [17]. Hormone-induced chromatin changes, in turn, can regulate the expression of large sets of genes [18].…”