We performed a comparative analysis of the effect of high-mobility group box protein 1 (HMGB1) on DNA binding by the DNA-binding domains (DBDs) of the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. The affinity of the DBDs of the different receptors for the tyrosine aminotransferase glucocorticoid response element, a classical high-affinity binding element, was augmente...

PURPOSE Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize. METHODS In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent)...

BACKGROUND Radical prostatectomy is used to treat patients with clinically localized prostate cancer, but there have been few reports of its use in locally advanced disease. We evaluated the long-term results of radical prostatectomy and immediate adjuvant androgen deprivation therapy in Japanese patients with pT3N0M0 prostate cancer. METHODS We retrospectively reviewed 128 patients with pT3N...

The nuclear receptor superfamily members of eukaryotic transcriptional regulators contain a highly conserved activation function 2 (AF2) in the hormone binding carboxyl-terminal domain and, for some, an additional activation function 1 in the NH(2)-terminal region which is not conserved. Recent biochemical and crystallographic studies revealed the molecular basis of AF2 is hormone-dependent rec...

Androgen independence is responsible for most prostate cancer lethality, yet currently there are no effective clinical treatments. We have been investigating the mechanisms underlying androgen-independent prostate cancer in Nkx3.1;Pten mutant mice, which display salient features of the disease, including a requirement for wild-type androgen receptor (AR) signaling. We now demonstrate that the A...

BACKGROUND Prostatic carcinoma is the most commonly diagnosed cancer and the second leading cause of cancer death of North American men. Combined androgen blockade (CAB) is one treatment option for prostate cancer, using estrogen agonists, luteinizing hormone-releasing hormone (LHRH) agonists and non-steroidal anti-androgens such as nilutamide and cyproterone acetate. Since many of these drugs ...

OBJECTIVE To describe the sources, production rates, circulating concentrations, and regulatory mechanisms of the major androgen precursors and androgens in women. DESIGN Review of the major published literature. RESULT(S) Quantitatively, women secrete greater amounts of androgen than of estrogen. The major circulating steroids generally classified as androgens include dehydroepiandrosteron...

BACKGROUND The aim of this study was to assess whether low serum testosterone levels in men with newly diagnosed prostate cancer have an association to the endocrine status, prostate-specific antigen (PSA) levels, Gleason score, and androgen receptor expression. METHODS Besides a full clinical work-up, the following hormones were quantified in men with newly diagnosed prostate cancer by serum...

Progression of prostate cancer ultimately results in a disease that is refractory to hormone ablation therapy but nevertheless continues to require the androgen receptor. Progression to hormone refractory disease is often correlated with overexpression of growth factors and receptors capable of establishing autocrine and/or paracrine growth-stimulatory loops. Many of these growth factor recepto...

BACKGROUND Although androgen withdrawal can control prostate cancer for long periods in many patients, controversy exists regarding management when the tumor becomes androgen independent. Several options are now available. METHODS A review of the pertinent literature of the last 20 years was conducted to provide guidance in defining and managing hormone-refractory prostate cancer. RESULTS S...