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.
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).
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.
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.
In other cases, altered androgen receptor activity due to its mutation or altered expression may lead to pathology such as recurrence of prostate cancer due to development of androgen independence allowing tumor cell proliferation under androgen deprivation.
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.
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.
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.
Here we review the role of the AR gene and its putative downstream effector pathways during human prostate cancer progression and endocrine therapy failure.
We have investigated the expression of AR and two prostate-specific androgen-responsive antigens, prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), for the functional activity of AR in LNCaP and PC-3 human prostate carcinoma cells.Our results are as follows.
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.
Because two potent antiandrogens, hydroxyflutamide (Eulexin), and bicalutamide (casodex), that are widely used for the treatment of prostate cancer, fail to block Adiol-mediated induction of AR transcriptional activity in prostate cancer cells, the effectiveness of so-called "total androgen blockage," a standard treatment for prostate cancer, may need to be reevaluated.
The conclusions are: (1) the sets of responses of cell proliferation to three androgen-receptor ligands are cell specific; (2) the control of c-myc messenger RNA by R 1881 and RU 56187 may be related to the inhibition of cell proliferation by these compounds but not to their stimulatory effect on cell proliferation; (3) if prostate tumor cells would respond in vivo to androgens and antiandrogens like in culture, patients with prostate cancer could take benefits of reversible medical castration and sequential prescription of various antiandrogens.