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AR Level (ar + level)
Selected AbstractsNitric oxide induces acrosome reaction in cryopreserved bovine spermatozoaANDROLOGIA, Issue 5 2005P. C. Rodriguez Summary The aim of this work was to study the effect of nitric oxide on acrosome reaction (AR) and the participation of protein kinases and reactive oxygen species in the AR of cryopreserved bovine spermatozoa. Spermatozoa were capacitated in Tyrode's albumin lactate pyruvate medium with heparin (10 IU ml,1) and then incubated with different concentrations of sodium nitroprusside (SNP) (1,200 ,mol l,1). Methylene blue and haemoglobin were used to confirm the role of nitric oxide as an inducer of the AR. The participation of protein kinase A (PKA) , protein kinase C (PKC) and protein tyrosine kinase was evaluated using specific inhibitors of these enzymes (H-89, 50 ,mol l,1; bisindolylmaleimide I, 0.1 ,mol l,1 and genistein, 3 ,mol l,1). The role of hydrogen peroxide or superoxide anion was evaluated by incubation with catalase or superoxide dismutase respectively. AR percentages were determined by the fluorescence technique with chlortetracycline. The highest levels of AR were obtained in capacitated spermatozoa treated with 5,200 ,mol l,1 SNP (24.8 ± 1.8%). The presence of PKA, PKC and protein tyrosine kinase inhibitors likewise decreased AR percentages. The addition of superoxide dismutase had no effect on the AR level but catalase completely blocked it. These results indicate that nitric oxide induces AR in capacitated spermatozoa involving hydrogen peroxide and the participation of PKA, PKC and protein tyrosine kinase as part of the signal transduction mechanism which lead to the AR in cryopreserved bovine spermatozoa. [source] Augmented suppression of androgen receptor signaling by a combination of ,-tocopheryl succinate and methylseleninic acidCANCER, Issue 12 2006Haitao Zhang PhD Abstract BACKGROUND. Previous reports showed that ,-tocopheryl succinate (,TS) and methylseleninic acid (MSA) independently reduce the abundance of androgen receptor (AR) in prostate cancer cells. The response to MSA happens quickly, whereas the response to ,TS takes much longer. The present study was designed to investigate whether a combination of ,TS and MSA would produce an additive or a greater than additive effect in suppressing AR level, AR transactivation, and prostate-specific antigen (PSA). METHODS. LNCaP cells were treated with ,TS alone for 31 hours, MSA alone for 3 hours, or ,TS first for 28 hours and ,TS/MSA together for the last 3 hours. AR and PSA mRNA levels were quantitated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). AR transactivation was determined by the ARE-luciferase reporter assay. Both cellular and secretory PSA was also measured by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS. Different doses of ,TS were evaluated in combination with MSA. Some striking results are highlighted below for ,TS alone, MSA alone, or ,TS/MSA (presented in that order). AR mRNA level was depressed by 0%, 20%, or 60%, respectively; AR transactivation was inhibited by 35%, 10%, or 60%, respectively; whereas the PSA mRNA level was decreased by 40%, 60%, or 90%, respectively. Interestingly, secretory PSA was consistently reduced to a greater extent than cellular PSA. CONCLUSIONS. A combination of ,TS/MSA produced a greater than additive effect in suppressing AR signaling compared with the single agent. Decreased AR abundance is a major factor, but not necessarily the sole factor, in diminishing the transcriptional activity of AR by ,TS or MSA. Cancer 2006. © 2006 American Cancer Society. [source] Decrease in stromal androgen receptor associates with androgen-independent disease and promotes prostate cancer cell proliferation and invasionJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2008Yirong Li Abstract Androgen receptor (AR) is expressed in both stromal and epithelial cells of the prostate. The majority of studies on AR expression and function in prostate cancer is focused on malignant epithelial cells rather than stromal cells. In this study, we examined the levels of stromal AR in androgen-dependent and -independent prostate cancer and the function of stromal AR in prostate cancer growth and invasion. We showed that stromal AR levels were decreased in the areas surrounding cancerous tissue, especially in androgen-independent cancer. Using two telomerase-immortalized human stromal cell lines, one AR-positive and the other AR-negative, we demonstrated that stromal cells lacking AR stimulated cell proliferation of co-cultured prostate cancer cells in vitro and enhanced tumour growth in vivo when co-injected with PC3 epithelial cells in nude mice. In contrast, stromal cells expressing AR suppressed prostate cancer growth in vitro and in vivo. In parallel with cancer growth, in vitro invasion assays revealed that stromal cells lacking AR increased the invasion ability of PC3 cell by one order of magnitude, while stromal cells expressing AR reduced this effect. These results indicate a negative regulation of prostate cancer growth and invasion by stromal AR. This provides potentially new mechanistic insights into the failure of androgen ablation therapy, and the reactivation of stromal AR could be a novel therapeutic approach for treating hormone refractory prostate cancer. [source] Calpain-mediated androgen receptor breakdown in apoptotic prostate cancer cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2008Huanjie Yang Since androgen receptor (AR) plays an important role in prostate cancer development and progression, androgen-ablation has been the frontline therapy for treatment of advanced prostate cancer even though it is rarely curative. A curative strategy should involve functional and structural elimination of AR from prostate cancer cells. We have previously reported that apoptosis induced by medicinal proteasome-inhibitory compound celastrol is associated with a decrease in AR protein levels. However celastrol-stimulated events contributing to this AR decrease have not been elucidated. Here, we report that a variety of chemotherapeutic agents, including proteasome inhibitors, a topoisomerase inhibitor, DNA-damaging agents and docetaxel that cause cell death, decrease AR levels in LNCaP prostate cancer cells. This decrease in AR protein levels was not due to the suppression of AR mRNA expression in these cells. We observed that a proteolytic activity residing in cytosol of prostate cancer cells is responsible for AR breakdown and that this proteolytic activity was stimulated upon induction of apoptosis. Interestingly, proteasome inhibitor celastrol- and chemotherapeutic drug VP-16-stimulated AR breakdown was attenuated by calpain inhibitors calpastatin and N -acetyl- L -leucyl- L -leucyl- L -methioninal. Furthermore, AR proteolytic activity pulled down by calmodulin-agarose beads from celastrol-treated PC-3 cells showed immunoreactivity to a calpain antibody. Taken together, these results demonstrate calpain involvement in proteasome inhibitor-induced AR breakdown, and suggest that AR degradation is intrinsic to the induction of apoptosis in prostate cancer cells. J. Cell. Physiol. 217: 569,576, 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||