Suppression of Estrogen Receptor Transcriptional Activity by Connective Tissue Growth Factor

Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER) that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF) physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs

The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease.

The miR-17/92 cluster is among the best-studied microRNA clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster\u27s involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members

Selective inhibition of BET bromodomain epigenetic signalling interferes with the bone-associated tumour vicious cycle

The vicious cycle established between bone-associated tumours and bone resorption is the central problem with therapeutic strategies against primary bone tumours and bone metastasis. Here we report data to support inhibition of BET bromodomain proteins as a promising therapeutic strategy that target simultaneously the three partners of the vicious cycle. Treatment with JQ1, a BET bromodomain inhibitor, reduces cell viability of osteosarcoma cells and inhibits osteoblastic differentiation both in vitro and in vivo. These effects are associated with transcriptional silencing of MYC and RUNX2, resulting from the depletion of BRD4 from their respective loci. Moreover, JQ1 also inhibits osteoclast differentiation by interfering with BRD4-dependent RANKL activation of NFATC1 transcription. Collectively, our data indicate that JQ1 is a potent inhibitor of osteoblast and osteoclast differentiation as well as bone tumour development

Micturition problems in relation to quality of life in men with prostate cancer or benign prostatic hyperplasia - Comparison with men from the general population

The aim of the study was to investigate men with prostate cancer and benign prostatic hyperplasia (BPH) in comparison with men from the general population in aspects of presence and frequency of micturition problems in remembrance of prior to treatment and currently. Further, the aim was to investigate the impact of micturition problems on quality of life and the association with micturition problems, and quality of life and sense of coherence (SOC). The samples consisted of 155 men with prostate cancer, 131 with BPH, and 129 from the general population. Micturition problems were assessed with study-specific questions, modified International Prostate Symptom Score (IPSS), quality of life questionnare (QLQ C-30), and SOC questionnaires. Parametric and nonparametric statistics were applied. Most troublesome urinary problems were leakage, feelings of discomfort, and disrupted urinary function and frequency. Men with urological diagnosis had more micturition problems, fatigue, and sleeping difficulties than men from the general population, but the cancer diagnosis did not add to the problems. Role and social functioning (prostate cancer), emotional functioning (BPH), and grade of fatigue (general population) showed itself vital for overall quality of life. Thus, help in solving issues of micturition problems, fatigue, and sleeping disturbances may contribute to maintenance of role, social, and emotional aspects of life

The handbook of credit and accounts receivable management/ Bukics

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