Download or read book Androgen Receptor and Integrin Regulation of Prostate Epithelial Differentiation and Tumor Cell Survival written by Laura Elaine Lamb and published by . This book was released on 2010 with total page 500 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Androgen Receptor and Integrin Regulation of Prostate Tumor Survival and Invasion written by Jelani Chinelo Zarif and published by . This book was released on 2014 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Androgen Action in Prostate Cancer written by Donald Tindall and published by Springer Science & Business Media. This book was released on 2009-04-20 with total page 782 pages. Available in PDF, EPUB and Kindle. Book excerpt: Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor. Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This book will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. Recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer will be included

Download or read book Molecular and Cellular Biology of Prostate Cancer written by James P. Karr and published by Springer Science & Business Media. This book was released on 1991 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: I. Intracellular Communications.- Tissue Specificity and Cell Death are Associated with Specific Alterations in Nuclear Matrix Proteins.- Mechanism of Growth Regulation in Androgen Responsive Cells.- The Impact of Androgen, Extracellular Matrix, and Stroma upon Proliferation and Differentiation of Benign and Malignant Prostate Epithelial Cells.- Therapeutic Approaches to Activating Programmed Cell Death of Androgen-Independent Prostatic Cancer Cells.- Cell Motility and Structural Harmonics in Prostate Cancer.- Panel Discussion.- II. Growth Factors - 1.- Studies of the Endocrine and Paracrine Effect of Tumor Produced Factors in Human Genitourinary Cancers.- Fibroblast Growth Factor: Implications in the Etiology of Benign Prostatic Hyperplasia.- Fibroblast-Mediated Human Epithelial Tumor Growth and Hormonal Responsiveness In Vivo.- Polyamine Requirement of Prostate Cancer Cell Proliferation.- Heparin-Binding (Fibroblast) Growth Factor/Receptor Gene Expression in the Prostate.- Characterization and Partial Purification of a Non - Heparin-Binding Prostate Growth Factor From Cancerous Human Prostate.- Panel Discussion.- Growth Factors - 2.- Transforming Growth Factor a: A Potential Autocrine Growth Regulator in Prostatic Carcinoma.- Prostatic Growth Factors (PrGFs) - From the Identification of Probasin to the Role of PrGFs.- Urogenital Sinus Derived Growth Inhibitory Factor.- Growth Factor Antagonists in Prostate Cancer: Suramin and Cytotoxic Polyamines as Potential Therapy.- Transforming Growth Factors in Human Prostate Cancer.- Gene Products as the Motivating Force in the Prostate Cell's Response to Androgens.- Panel Discussion.- III. Steroid Receptors.- Molecular Biology of Prostate - Specific Antigen.- Structure and Expression of the Androgen Receptor in Normal Tissues and in Prostate Carcinoma Cell Lines.- Structural Analysis and Gene Expression of TR2 Receptor and TR3 Receptor.- cDNA Cloning, Antibody Production and Immunohistochemical Localization of the Androgen Receptor.- New Approaches to Studies on the Androgen Receptor.- Specific Receptors for Vitamin D3 in Human Prostatic Carcinoma Cells.- Panel Discussion.- IV. Poster Presentations.- Role of Androgens and Extracellular Matrix in the Growth and Differentiation of Benign and Malignant Prostatic Epithelial Cells.- Tissue Specificity and Cell Death Are Associated with Specific Alterations in Nuclear Matrix Proteins.- ElTect of Transformation on Rat Prostatic Fibroblasts: Alterations In Extracellular Matrix and Cytoskeleton Gene Expression with Retention of Androgen Responsiveness and Androgen Receptor Expression.- A Potential Role for the MDR-1 Gene in the Development of Androgen-Independent Tumors.- Relevance of Low Androgen Levels and Adrenal Androgens in the Growth of Transplantable Human Prostatic Carcinomas.- Growth-Stimulating Effect of Growth Factor(s) from Androgen Independent Tumor Cells (CS 2-Cell) on Androgen Responsive Tumor Cells.- The Cellular Form of Human Prostatic Acid Phosphatase May Function as a Phosphotyrosyl Protein Phosphatase in Cells.- Expression of Prostate Antigen in LNCaP Cells in Culture.- Allelic Expression of the Mouse Ren-1 Genes in the Anterior Prostate (Coagulating Gland).- V. Dna Structure and Gene Expression.- Genomic Alterations in Prostatic Cancer.- Regulation of Gene Expression in the Prostate.- Androgen Regulation of HBGF I-(aFGF) and Characterization of the Androgen-Receptor mRNA in the Human Prostate Carcinoma Ceil Une - LNCaP/A-dep.- DNA Methylation, Differentiation and Cancer.- Evidence for tbe Involement of Genetic Differences and Mesenchymal Factors in the Progression of Oncogene - Induced Prostate Cancer in Reconstituted Mouse Prostate.- Differential Hybridization Analysis as a Tool to Study Prostatic Cancer Metastasis.- Molecular Biology of Androgen Acceptors in Prostatic Cancer Cells.- Panel Discussion.- Panel Discussion.- Panel Discussion.- Panel Discussion.- Panel Discussion.- Contributors.

Download or read book Prostate Cancer Clinical And Scientific Aspects Bridging The Gap written by Paul David Abel and published by World Scientific. This book was released on 2003-12-01 with total page 1255 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite the advent of the genomic era, the perceived benefits of close collaboration between clinicians and scientists are not always realised and the gap between bench and bedside remains. Closer collaboration should expedite advances in treating disease. This important book, with a foreword by Fritz H Schröder, is designed to enhance the relationship between the two communities. It contains data from a multinational authorship, the thirty-eight chapters being written by experts with widely differing training and expectations. Their aim is to facilitate both understanding and in-depth knowledge of their subject. By bridging the gap between clinicians and scientists, the hope is to enhance translational research in their common goal of improving the diagnosis and treatment of prostate cancer, the single most important cancer affecting men./a

Download or read book Androgen Responsive Genes in Prostate Cancer written by Zhou Wang and published by Springer Science & Business Media. This book was released on 2013-02-16 with total page 347 pages. Available in PDF, EPUB and Kindle. Book excerpt: Androgens and androgen receptors (AR) play critical roles in the development and progression of prostate cancer, the most frequently diagnosed cancer and second leading cause of cancer death in US males. AR is an androgen-dependent DNA-binding transcription factor that regulates the expression of androgen-responsive genes. Identification and characterization of androgen-responsive genes provide insights into the cellular mechanisms of androgen action and may lead to new approaches in diagnosis, prognosis, prevention and/or treatment of prostate cancer. This volume provides critical information from well respected experts in the field. Some of the exciting topics include the new understanding of mechanisms underlining the regulation of androgen-responsive gene expression, and functions of various androgen-responsive genes in biological processes essential in carcinogenesis including cell growth, angiogenesis, and epithelial-to-mesenchyme transition (EMT). Other important aspects addressed are the current and potential clinic applications of knowledge on androgen-responsive gene regulation and function. This book is intended for researchers, scientists, faculty, and advanced graduate students with an interest in androgen action and prostate cancer.​

Download or read book Function of an Androgen Receptor Coactivator Regulated in Prostate Development and Prostate Cancer written by and published by . This book was released on 2005 with total page 11 pages. Available in PDF, EPUB and Kindle. Book excerpt: We hypothesize that ART-27 affects AR-dependent differentiation of prostate epithelial cells by regulating a subset of AR responsive genes important to prostate growth suppression and differentiation. We further hypothesize that alterations in the level of ART-27 modulates AR activity, which, in turn, affects AR-dependent cell growth regulation in vivo. Our aims are to identify ART-27-dependent AR-target genes involved in growth suppression and differentiation and to elucidate the mechanism of regulation of ART-27 expression in prostate cancer. Our approach is to ablate ART-27 protein using siRNA technology followed by gene expression array. Our preliminary findings indicate that loss of ART-27 may result in enhanced expression of genes that are often over-expressed in prostate cancer such as PSA, FKBP5, SOR, KRT18, and CDKN3. Loss of ART-27 also shows enhanced expression of at least one positive regulator of tumor growth, CDKN3.

Download or read book The Integrin Regulated Jinase PYK 2 A Therapeutic Target for Prostate Cancer written by and published by . This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: A prostate cancer cell's growth differentiation and survival are guided by its interactions with the surrounding extracellular matrix (ECM). A number of promising therapeutic targets for androgen-independent and metastatic prostate cancers are contained within the signaling cascades downstream of the ECM-binding Integrin molecules. My research focuses on one component of these cascades, the phosphotyrosine kinase PYK-2, whose expression levels and activity I aim to manipulate in cell culture and within tumors in mice, using constitutively-active and dominant-negative PYK-2 constructs under the control of tetracycline-inducible promoters. Such regulation of PYK-2 may provide a means of pushing cells forward or backward in cancerous progression. By monitoring changes in the behaviors of cells expressing PYK-2 mutant variants, in the presence and absence of integrin-stimulating and blocking factors, we are simultaneously studying the downstream role of PYK-2 in regulating cell behaviors, and the upstream role of integrins in regulating PYK-2. Finally, we will introduce the PYK- 2-construct-expressing cells into adult mice, that we treat with tetracycline at different times during tumor development, castrate or leave whole, and monitor for tumor progression and necrosis. An extremely valuable tool in these studies will be the lineage- related LNCaP cell lines, developed in our laboratory, each of which represents a stage in prostate cancer cell progression, from marginally-tumorigenic and androgen-sensitive, to highly-metastatic and androgen- insensitive. If intentional PYK-2 modulation proves sufficient to control LNCaP model cell proliferative, migratory or apoptotic behaviors, our laboratory is uniquely equipped to develop the approach into a clinical therapy, by delivering the genes in an adenoviral vector, first to LNCaP tumors in mice, and eventually to men.

Download or read book Mechanism and Regulation of Gene Expression by Androgen Receptor in Prostate Cancer written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our general objective is to use completely defined cell-free transcription systems both to identify novel AR-associated cofactors and to investigate the mechanism of action of AR and both novel and previously identified candidate coactivators. To this end, we have expressed and purified 5 AR-associated cofactors and established a chromatin assembly system to study AR function with chromatin template. We have shown an enhancement of AR function by the TRAP/Mediator coactivator complex that is generally utilized by a number of different nuclear receptors. Relevant to the mechanism involved, we have identified two TRAP/Mediator subunits as potential targets for the liganded AR receptor. The expression of AR and 10 cofactors by quantitative in situ RNA hybridization in 44 primary prostate cancers with different degree of differentiation was investigated. Our results revealed near constant expression of AR and heterogeneous expression of AR cofactors. Expression of PIAS1 and Ran/ARA24 was increased and expression of ELEl/ATRA70 was decreased. In addition, we demonstrated that the human prostate tumor cell proliferation and colony formation are markedly reduced by over-expression of ELEl/ARA70. Together, these findings indicate that the change of expression levels of AR cofactors may play important roles in prostate growth and tumorigenesis.

Download or read book Integrin Mediated Signaling in Prostate Cancer Role of KAI1 CD82 in Regulating Integrin and Androgen Receptor Function During Metastasis written by and published by . This book was released on 2007 with total page 64 pages. Available in PDF, EPUB and Kindle. Book excerpt: How prostate tumors become metastatic is virtually unknown. A prostate metastasis suppressor gene, KAI1/CD82, known to associate with laminin receptors, allowed us to test the hypothesis that loss of KAI1/CD82 expression alters the function of laminin integrins in prostate cancer cells, resulting in altered intracellular signaling and increased invasion leading to metastasis. We have demonstrated that in metastatic tumor cells, where elevated c-Met expression and activation by integrins is responsible for enhancing laminin-dependent migration and invasion, re-expression of CD82 suppresses, while loss of CD82 enhances c-Met activation. Orthotopic injection of CD82-expressing metastatic cells into mouse prostates suppresses both metastasis and growth in vivo. CD82 appears to regulate c-Met activation by altering the distribution of c-Met on the cell surface, possibly through CD82 association with another tetraspanin, CD9, and their joint association with PI integrin. Our studies have advanced the knowledge of how members of the tetraspanin family function and are potentially applicable to all metastatic disease, since KAI1/CD82 loss has been reported in many types of cancers. Our results suggest that targeting c-Met would be a logical approach to therapeutic intervention of metastatic disease. Our findings further suggest that together CD82 expression and c-Met activation could be used as a potential biomarker pair for the prediction of metastatic disease. In addition we have shown that the PI-3K/Akt pathway is critical for laminin-specific survival in metastatic prostate cells, but activation of the androgen receptor (AR) by-passes the need for PI-3K signaling when cells are adherent to laminin. Since over 90% of metastatic prostate cancers still express AR, targeting the PI-3K pathway alone would not be sufficient to kill tumors in a laminin-rich environment.

Download or read book Molecular Mechanisms of Prostate Cancer Progression and Treatment Resistance written by Yezi Zhu and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer is the most common type of cancer in American men and ranks second to lung cancer in cancer-related deaths. The growth and survival of primary prostate tumors requires physiological level of androgen. Thus hormone therapy has been used for treatment of primary prostate cancer. However, prostate cancer eventually progresses to a castration-resistant state. Understanding the molecular mechanisms leading to castration resistance is very critical for combat this lethal disease. The first part of this thesis will discuss the loss of Rho-GDP dissociation inhibitor [alpha] (RhoGDI[alpha]) as one of the molecular mechanisms leading to prostate cancer castration-resistant progression. My study demonstrated that RhoGDI[alpha] suppresses growth and survival of prostate cancer cells. In this part, I utilized the previously generated LNCaP-IL6+ cells which were able to grow in androgen-deprived condition. The protein expression profiles of LNCaP and LNCaP-IL6+ cells were compared using two-dimensional gel electrophoresis. Expression of RhoGDI[alpha] was reduced in LNCaP-IL6+ cells and was down-regulated in more aggressive prostate cancer cells compared to LNCaP cells. The effects of RhoGDI[alpha] in prostate cancer cells growth and survival were examined both in vitro and in vivo. Overexpression of RhoGDI[alpha] inhibited the growth and induced apoptosis of prostate cancer cells. RhoGDI[alpha] caused LNCaP-IL6+ cells reversal to androgen-sensitive state, and downregulation of RhoGDI[alpha] enhanced growth of androgen-sensitive LNCaP cells in androgen-deprived condition. In addition, RhoGDI[alpha] suppressed the tumorigenic ability and prostate-specific antigen (PSA) production of prostate tumor xenografts in vivo. The aberrant activation of androgen receptor (AR) is responsible for castration-resistant prostate cancer (CRPC) progression and regulation of AR-target genes such as PSA. My in vivo study showed RhoGDI[alpha] inhibited PSA production in the mice sera bearing tumors, indicating RhoGDI[alpha] inhibits AR signaling in prostate cancer cells. The effects of RhoGDI[alpha] on AR signaling will be further discussed. RhoGDI[alpha] was transiently or stably transfected into several prostate cancer cell lines including LNCaP, C4-2, CWR22Rv1 and DU145. The regulation of AR expression by RhoGDI[alpha] was analyzed by qRT-PCR and Western blot. Overexpression of RhoGDI[alpha] downregulated AR expression at both mRNA and protein levels. AR activity was measured by luciferase reporter assays and electrophoretic mobility shift analysis (EMSA). RhoGDI[alpha] was able to inhibit transactivation of AR target genes and prevent AR binding to androgen response element. Immunofluorescence assay was performed and overexpression of RhoGDI[alpha] prevented AR nuclear translocation induced by androgens. The interaction between RhoGDI[alpha] and AR was examined by co-immunoprecipitation assays. RhoGDI[alpha] was found to physically interact with the N-terminal domain of AR. Neuroendocrine differentiation (NED) is associated with castration-resistance of prostate cancer. It has been suggested as a marker of poor prognosis for prostate cancer. Paracrine interleukin-6 (IL-6) can mediate NED features in prostate cancer. The second part of this thesis will discuss the mechanism underlying IL-6-induced NED. RE1-silencing transcription factor (REST) is a main negative regulator of neurogenesis and represses expression of NED genes. I confirmed the IL-6-induced NED by cell morphological changes as well as the induction of NE markers such as neuron-specific enolase (NSE), chromogranin A (ChgA) and synaptophysin. The expression of REST was suppressed in IL-6-induced NED in LNCaP cells. To further study the impact of REST-mediated repression on NED in LNCaP cells, either wild-type REST or a dominant-positive form of REST, REST-VP16, in which both repressor domains of REST were replaced with the activation domain of the herpes simplex virus protein VP16, was introduced into LNCaP cells. Overexpression of exogenous wild type REST abrogated IL-6-induced NED in prostate cancer cells. Expression of the recombinant REST-VP16 fusion protein activated REST target genes and other neuronal differentiation genes and produced neuronal physiological properties. In addition, REST protein turnover was accelerated in IL-6 induced NE differentiated LNCaP cells via the ubiquitin-proteasome pathway, accompanied by a decrease in the expression of the deubiquitylase HAUSP, indicating that pathway(s) priming REST degradation may be involved in IL-6 induced NE differentiation. Docetaxel is the first-line standard treatment for CRPC. However, once tumors develop resistance to docetaxel, the treatment options are again limited. In the last part of this thesis, I will discuss the docetaxel resistance mechanisms and potential therapeutic strategies for docetaxel-resistant CRPC. I established a docetaxel resistant cell line, TaxR, by culturing C4-2B cells in docetaxel in a dose-escalation manner until cells were able to divide freely in 5 nM docetaxel. Global gene expression analysis by cDNA microarrays (approximately 28000 genes) was performed using mRNA from parental C4-2B and TaxR cells. ABCB1, which belongs to the ATP-binding cassette (ABC) transporter family, was identified among the top upregulated genes in TaxR cells. Overexpression of ABCB1 in TaxR cells has been validated by both real-time PCR and Western blot analysis. Downregulation of ABCB1 by specific shRNA or inhibiting ABCB1 activity by ABCB1 inhibitor elacridar restored docetaxel sensitivity in TaxR cells. Apigenin (4', 5, 7-trihydroxyflavone), a natural product belonging to the flavone family, downregulated ABCB1 protein expression in ubiquitin-proteasome pathway and overcame docetaxel resistance in TaxR cells. The effects of different anti-androgens like enzalutamide, abiraterone and bicalutamide on ABCB1 efflux activity were tested using rhodamine123 efflux assay. These antiandrogens inhibited ABCB1 efflux activity and reversed docetaxel resistance in TaxR cells in vitro. The reversal effect of bicalutamide was further confirmed in TaxR xenograft tumors, suggesting targeting ABCB1 could be a potential approach to resensitize docetaxel-resistant prostate cancer cells to docetaxel treatment.

Download or read book Molecular Biology of Prostate Cancer written by Manfred Wirth and published by Walter de Gruyter. This book was released on 2013-05-22 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Epithelial Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.

Download or read book Leong s Manual of Diagnostic Antibodies for Immunohistology written by Runjan Chetty and published by Cambridge University Press. This book was released on 2016-11-28 with total page 525 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing a unique A-Z guide to antibodies for immunohistology, this is an indispensable source for pathologists to ensure the correct application of immunohistochemistry in daily practice. Each entry includes commercial sources, clones, descriptions of stained proteins/epitopes, the full staining spectrum of normal and tumor tissues, staining pattern and cellular localization, the range of conditions of immunoreactivity, and pitfalls of the antibody's immunoprofile, giving pathologists a truly thorough quick-reference guide to sources, preparation and applications of specific antibodies. Appendices provide useful quick-reference tables of antibody panels for differential diagnoses, as well as summaries of diagnostic applications. Expanded from previous editions with over forty new entries, this handbook for diagnostic, therapeutic, prognostic and research applications of antibodies is an essential desktop book for practicing pathologists as well as researchers, residents and trainees.

Download or read book The Epithelial to Mesenchymal Transition written by Kyra Campbell and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book New Prognostic and Predictive Markers in Cancer Progression written by Susan Costantini Alfredo Budillon and published by MDPI. This book was released on 2021-02-12 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biomarkers are of critical medical importance for oncologists, allowing them to predict and detect disease and to determine the best course of action for cancer patient care. Prognostic markers are used to evaluate a patient’s outcome and cancer recurrence probability after initial interventions such as surgery or drug treatments and, hence, to select follow-up and further treatment strategies. On the other hand, predictive markers are increasingly being used to evaluate the probability of benefit from clinical intervention(s), driving personalized medicine. Evolving technologies and the increasing availability of “multiomics” data are leading to the selection of numerous potential biomarkers, based on DNA, RNA, miRNA, protein, and metabolic alterations within cancer cells or tumor microenvironment, that may be combined with clinical and pathological data to greatly improve the prediction of both cancer progression and therapeutic treatment responses. However, in recent years, few biomarkers have progressed from discovery to become validated tools to be used in clinical practice. This Special Issue comprises eight review articles and five original studies on novel potential prognostic and predictive markers for different cancer types.

Download or read book Heat Shock Proteins in Cancer written by Stuart K. Calderwood and published by Springer Science & Business Media. This book was released on 2007-09-09 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.