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Androgen Responsiveness (androgen + responsiveness)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

NF-,B2/p52 enhances androgen-independent growth of human LNCaP cells via protection from apoptotic cell death and cell cycle arrest induced by androgen-deprivation

THE PROSTATE, Issue 16 2008
Nagalakshmi Nadiminty
Abstract PURPOSE Androgen-deprivation therapy only causes a temporary regression of prostate cancer, as all tumors will eventually progress to refractory to hormonal therapy after 1,3 years of treatment. The underlying mechanisms of prostate cancer androgen refractory progression are incompletely understood. In this study, we employed in vitro as well as in vivo models to examine the role of NF-,B2/p52 in prostate cancer growth and androgen independent progression. EXPERIMENTAL DESIGN The effects of NF-,B2/p52 on cell growth, androgen responsiveness, cell cycle and apoptosis were examined in androgen sensitive LNCaP cells. The effect of NF-,B2/p52 on tumor growth was examined in intact and castrated male mice. RESULTS Overexpression of NF-,B2/p52 enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic ability in androgen-deprived condition in vitro. NF-,B2/p52 induced androgen-independent growth is through protecting LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. In addition, NF-,B2/p52 stimulates Cyclin D1 expression and knock down of Cyclin D1 expression by siRNA abolished NF-,B2/p52-induced cell growth in vitro. Adenoviral mediated NF-,B2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-,B2/p52 induces androgen-independent growth of androgen-sensitive LNCaP cells. CONCLUSIONS Overexpression of NF-,B2/p52 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. NF-,B2/p52 activation induces androgen-independent growth in vitro and in vivo. Prostate © 2008 Wiley-Liss, Inc. [source]

Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells,

THE PROSTATE, Issue 10 2006
Z. Wu
Abstract BACKGROUND Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is lost as a function of prostate tumor androgen dependence. While the transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is unclear. METHODS We developed a system where PTEN can be conditionally re-expressed at physiologic levels into a PTEN null metastatic human CaP cell line, C4-2, and androgen responsiveness examined. RESULTS PTEN induction reduces cell growth and blocks the growth effect of synthetic androgen R1881. The anti-androgen Casodex enhances the growth-inhibitory action of PTEN and this effect is independent of Akt phosphorylation. Combined PTEN induction and Casodex, result in a further decrease in prostate specific antigen promoter activity compared to PTEN but not Casodex alone. CONCLUSIONS PTEN induction confers androgen independent CaP cells enhanced responsiveness to the anti-proliferative effects of anti-androgens and this action may involve non-AR mediated effects. Prostate 66: 1114-1123, 2006. © 2006 Wiley-Liss, Inc. [source]

Prolonging androgen sensitivity in prostate cancer , a role for COX inhibitors?

ANZ JOURNAL OF SURGERY, Issue 9 2009
Andrew Richards
Abstract Background:, Advanced prostate cancer has long been known to respond to androgen deprivation, but disease inevitably progresses to become androgen independent. Lengthening the responsive period is an important, yet underinvestigated, clinical goal. This study aims to determine whether cyclooxygenase-2 (COX-2) inhibitors are potentially useful agents in prolonging androgen sensitivity. Methods:, The expression of COX-2 in human prostate surgical specimens, both benign and malignant, androgen dependent and independent, was determined by immunohistochemistry. Nude mice, in which prostate cancer xenografts had been established, were castrated and randomized to receive either COX-2 inhibitor or vehicle for 8 weeks. Time to androgen independence (AIPC), growth rate and rate of PSA rise were compared between groups. COX-2 expression, at the mRNA and protein level, was determined in the native xenograft cell line and in tissues of varying androgen sensitivity derived from the xenografts. Results:, In human tissues, COX-2 protein was expressed in prostate epithelium and was upregulated in prostate cancer and remained upregulated after androgen ablation and in the androgen-independent state. Tissue obtained from the LNCaP xenograft model showed variable COX-2 expression, with some evidence of downregulation in AIPC. The addition of a COX-2 inhibitor to castration does not lengthen the time to AIPC (P= 0.53), rate of tumour growth (P= 0.59) or rate of PSA rise (P= 0.34) in the LNCaP xenograft model. Conclusion:, This study does not support a role for COX-2 inhibitors in prolonging androgen responsiveness in prostate cancer. [source]