Intranuclear Androgen Receptor Deployment and Protooncogene Expression in Human Diseased Prostate

Abstract

Androgen receptors were quantified in nuclei from human prostate tissue and in nuclear fractions derived by exhaustive digestion with micrococcal nuclease. In nuclei from benign hypertrophic prostate (BPH), the population of androgen receptors solubilized during nucleolysis predominated whereas in carcinoma nuclei the nuclease-resistant population was in excess. This phenomenon was restricted to intranuclear deployment and could not be attributed to recompartmentalization within the cell. Receptor content could not be correlated to the expression of the cellular protooncogenes myc, H-ras, K-ras or sis, in either BPH or carcinoma. However, in both BPH and carcinoma, significant correlation was observed between nuclear androgen receptor content and expression of c-fos. Expression of c-fos was not elevated in carcinoma compared to BPH, whereas expression of c-myc was elevated in carcinoma specimens of all grades of glandular differentiation, and expression of H-ras became increasingly elevated as differentiation was lost.

Human prostate cancer risk factors

“…Some studies have failed to identify c‐ myc gene amplification1127 or an association with grade1332 and stage,1333 but most reports suggest that it plays a role in the regulation of prostate growth and carcinogenesis. Despite early studies demonstrating elevated expression of c‐ myc in all grades of cancer1334 or predominantly in tumors with a Gleason score > 5,683 current belief is that there is substantial amplification with increasing grade of cancer, particularly in metastases 809. Moreover, transfection with c‐ myc and ras induces carcinogenesis of the murine prostate 677.…”

Genetic aspects of prostate cancer

“…PDGF-A and its receptor are upregulated in prostate adenocarcinomas [64]. The PDGF-B polypeptide chain, encoded by the proto-oncogene SIS, is also over-expressed in androgen-independent prostate cancer cell lines [189] and poorly differentiated tumours [166]. However, further studies are required to assess the role of PDGF in prostate oncogenesis.…”

Prostatic Cancer: Aetiology and Endocrinology

“…Similar positive correlations between the expression of the oncogene c-myc and increasing levels of tumour dedifferentiation have also been noted. Con versely, c-fos expression has been correlated with welldifferentiated, androgen receptor positive cancers [30]. Such parameters may provide the basis for more effective prognostic indices.…”