Overexpression of the HER2/Neu protooncogene has been linked to progression breast cancer. Here we demonstrate that growth prostate cancer LNCaP cells can also be increased by stable transfection HER2/Neu. Using AG879, a inhibitor, and PD98059, MAP kinase as well phosphatase-1 (MPK-1), in assay, found could induce prostate-specific antigen (PSA), marker for cancer, through pathway at low androgen level. Reporter assays mammalian two-hybrid further suggest this HER2/Neu-induced receptor (AR)...

Whereas several apoptosis-related proteins have been linked to the antiapoptotic effects of Akt serine–threonine kinase, search continues explain signaling role in promoting cell survival via effects. Here, we demonstrate that phosphorylates androgen receptor (AR) at Ser-210 and Ser-790. A mutation AR results reversal Akt-mediated suppression transactivation. Activation phosphatidylinositol-3-OH kinase/Akt pathway target genes, such as p21, decrease androgen/AR-mediated apoptosis, which may...

The information of protein targets and small molecule has been highly valued by biomedical pharmaceutical research. Several target databases are available online for FDA-approved drugs as well the promising precursors that have largely facilitated mechanistic study subsequent research drug discovery. However, those related resources regarding to herbal active ingredients, although being unusually a precious resource new development, is rarely found. In this article, comprehensive fully...

Androgen receptor (AR) is a hormone-activated transcriptional factor that can bind to androgen response elements and regulates the transcription of target genes via mechanism presumably involves cofactors. We report here cloning novel AR coactivator ARA55 using yeast two-hybrid system. consists 444 amino acids with predicted molecular mass 55 kDa its sequence shows very high homology mouse hic5, TGF-β1-inducible gene. Yeast mammalian systems co-immunoprecipitation assays all prove in...

Androgen receptor (AR) is a member of the steroid superfamily that may require coactivators for proper or maximal transactivation. Using yeast two-hybrid screening followed by mammalian cell analyses, we identified novel ligand-dependent AR-associated protein, ARA54, which consists 474 amino acids with molecular mass 54 kDa. We demonstrated ARA54 might function as preferential coactivator AR-mediated transactivation in human prostate cancer DU145 cells. Interestingly, our data also showed...

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway controls several important biological functions, such as cell growth regulation, apoptosis, and migration. However, the way in which PI3K/Akt androgen receptor (AR)-mediated prostate cancer remains unclear controversial. Here, we demonstrate that regulates AR activity a passage number-dependent manner. Specifically, can suppress androgen-dependent LNCaP cells with low numbers. In contrast, it also enhance high Furthermore, insulin-like...

Recent studies suggest that miR-146b deregulation in papillary thyroid carcinoma (PTC) was associated with advanced tumor characteristics. However, the influence of expression on prognosis PTC remains unknown. We sought to correlate levels a previously reported cohort and reveal underlying mechanisms via cell line model. Expression were assessed quantitative real-time PCR 71 cases distinct clinico-pathogenetic All patients classified into disease-free or active disease group, based their...

Although mutations of the breast cancer susceptibility gene 1 (BRCA1) may play important roles in and prostate cancers, detailed mechanism linking functions BRCA1 to these two hormone-related tumors remains be elucidated. Here, we report that interacts with androgen receptor (AR) enhances AR target genes, such as p21 (WAF1/CIP1) , result increase androgen-induced cell death cells. The BRCA1-enhanced transactivation can further induced synergistically coregulators, CBP, ARA55, ARA70....

Although transforming growth factor-β (TGF-β) has been identified to mainly inhibit cell growth, the correlation of elevated TGF-β with increasing serum prostate-specific antigen (PSA) levels in metastatic stages prostate cancer also well documented. The molecular mechanism for these two contrasting effects TGF-β, however, remains unclear. Here we report that Smad3, a downstream mediator signaling pathway, functions as coregulator enhance androgen receptor (AR)-mediated transactivation....

The retinoblastoma protein may function as a tumor suppressor by controlling the progression of normal cell cycle. Inactivation Rb has been regarded an important event in prostate carcinogenesis. However, detailed mechanism how is linked to androgen-androgen receptor (A-AR), major factor promotion growth, remains unclear. Using GST-Rb pull down assay and mammalian two-hybrid system, we report here that can bind specifically AR androgen-independent manner. Transient transfection demonstrates...

Intraprostatic injection of BTX-A has demonstrated clinical improvement in men with bladder outlet obstruction. We investigated the mechanisms action on prostate.Adult male Sprague-Dawley rats were injected varying doses into prostate and prostates harvested after 1 or 2 weeks. The effects histology, proliferative apoptotic indexes determined using hematoxylin eosin staining, cell nuclear antigen staining TUNEL respectively. Changes alpha(1A) adrenergic receptor androgen evaluated by Western...

Abnormalities in Toll-like receptor (TLR) expression depression have been inferred part from observed increases TLR4 levels peripheral blood mononuclear cells (PBMCs) and postmortem brains of depressed suicidal patients. Our previous study found differences the TLR PBMCs between healthy controls patients with major depressive disorder. Normalization increased by cognitive behavior psychotherapy has reported. However, effects antidepressants remain unknown.Changes TLR1-9 were examined 56 MDD....

Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR MDD. This study aimed to assess association between severity of depression intracellular microRNAs regulate TLR4 both peripheral blood mononuclear cells (PBMCs) monocytes from MDD patients. The before after antidepressant treatment was determined by 17-item Hamilton Depression Rating...

The intracellular microRNAs that negatively regulate Toll-like receptor 4 signaling pathways in peripheral blood mononuclear cells are associated with major depressive disorder (MDD). However, the distribution of these exosomes could be a biomarker central nervous system diseases is just beginning to explored. In present study, we isolated serum from patients MDD and healthy controls explore levels exosomal microRNAs, including let-7e, miR-21-5p, miR-223, miR-145, miR-146a, miR-155. We also...

Androgens have important effects on the bone metabolism. However, effect and mechanism of androgen action osteoblasts remains unknown. Here we showed that androgens increase phosphorylation nuclear translocation Akt. siRNA-AR prevented androgen-induced Akt activation in MC3T3-E1 cells. This suggests nongenomic is mediated by receptor osteoblasts.Androgens human skeleton both males females. metabolism The aims this study were to determine osteoblast cells.Here 5alpha-dihydrotestosterone (DHT)...

Smad proteins have been demonstrated to be key components in the transforming growth factor β signaling cascade. Here we demonstrate that Smad4, together with Smad3, can interact androgen receptor (AR) DNA-binding and ligand-binding domains, which may result modulation of 5α-dihydrotestosterone-induced AR transactivation. Interestingly, prostate PC3 LNCaP cells, addition Smad3 enhance transactivation, co-transfection Smad4 then repress transactivation various response element-promoter...

DNA damage response is an important surveillance mechanism used to maintain the integrity of human genome in genotoxic stress. Histone variant H2AX a critical sensor that undergoes phosphorylation at serine 139 upon stress, which provides docking site recruit mediator checkpoint protein 1 (MDC1) and repair complex sites breaks for repair. Here, we show monoubiquitination induced double strand plays role Ser-139 (γ-H2AX), turn facilitating recruitment MDC1 foci. Mechanistically, by RING...

Inflammation and abnormalities in Toll-like receptor (TLR) expression activation have been linked to major depressive disorder (MDD). However, negative regulators of TLR pathways not previously investigated this context. Here, we sought investigate the association depression severity, measured by 17-item Hamilton Depression Rating Scale (HAMD-17), with mRNA levels pathway, including SOCS1, TOLLIP, SIGIRR, MyD88s, NOD2 TNFAIP3, peripheral blood mononuclear cells (PBMCs) from 100 patients MDD...