Some AR mutations in prostate cancer show broadened ligand specificity, such that the transcription-factor activity of the AR can be stimulated not just by dihydrotestosterone (DHT) but also by estradiol and other androgen metabolites that have a low affinity for the AR.
To evaluate the hypothesis that amplification of the AR gene is a cause for the failure of androgen deprivation therapy in prostate cancer, we studied whether AR amplification leads to gene overexpression, whether the amplified AR gene is structurally intact, and whether tumors with AR amplification have distinct biological and clinical characteristics.
These results demonstrate that a shorter CAG repeat sequence in the androgen receptor gene predicts higher grade and advanced stage of prostate cancer at diagnosis, and metastasis and mortality from the disease.
Androgenic induction of prostate-specific antigen gene is repressed by protein-protein interaction between the androgen receptor and AP-1/c-Jun in the human prostate cancer cell line LNCaP.
Expression of suicidal genes in prostate cancer cells using prostate-specific promoter and enhancer elements as well as targeting of the androgen receptor or the insulin-like growth factor genes with triplex technology in prostate cancer cells and their metastases, is expected to be of therapeutic value.
Fifty-seven non-Hispanic white case patients with prostate cancer and 169 non-Hispanic white control subjects were genotyped for a previously described microsatellite (CAG repeats) in the AR gene and for a newly discovered poly-A microsatellite in the 3'-untranslated region (3'UTR) of the VDR gene.
These data suggest that determination of both androgen receptor repeats within germ-line DNA may be useful in assessing an individual's risk of developing prostate cancer.
SfaNI digestion of AR exon H DNA from normal but not from prostate cancer tissue indicated H874Y is a somatic mutation that occurred before the initial tumor transplant.
Although 5'UTR mutations in the AR gene might only rarely occur in men with prostate cancer, the occasional mutation in this area may contribute to the disease by altering rates of transcription and/or translation of this gene.
Specimens from both a primary and a subsequent locally recurrent tumor were studied for amplification of the AR gene by fluorescence in situ hybridization from a prostate cancer patient who experienced tumor progression after monotherapy with the potent antiandrogen bicalutamide (Casodex, a trade mark, the property of Zeneca Ltd).
We have examined the inhibitory effect of rStd on androgen action in the human prostate cancer-derived PC-3 cells transfected with the rat androgen receptor (AR) expression plasmid and two androgen-responsive promoter reporter constructs (murine mammary tumor long-terminal repeat ligated to chloramphenicol acetyltransferase (CAT) gene and rat probasin androgen response element (ARE) ligated to firefly luciferase (LUC) gene).
Similarly, certain genetic polymorphisms of genes encoding for 5alpha-reductase, androgen receptor or vitamin D, have been associated with different levels of CaP risk, and could explain the variations observed between populations.
We investigated whether AR gene GGN repeat length is related to prostate cancer in a nested study of 582 cases and 794 controls matched on age and smoking status in the Physicians' Health Study.DNA was prepared from archived blood.
Development of an androgen receptor-null model for identifying the initiation site for androgen stimulation of proliferation and suppression of programmed (apoptotic) death of PC-82 human prostate cancer cells.