Understanding The Role Of Estrogen Receptor Beta In Triple Negative Breast Cancers

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Understanding the Role of Estrogen Receptor Beta in Triple Negative Breast Cancers

Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (865 download)

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Book Synopsis Understanding the Role of Estrogen Receptor Beta in Triple Negative Breast Cancers by :

Download or read book Understanding the Role of Estrogen Receptor Beta in Triple Negative Breast Cancers written by and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen signaling is primarily mediated by two estrogen receptors (ERs), ERÎI and ERÎø. ERÎI is expressed in ~70% of breast cancers and is an important diagnostic and therapeutic target. Approximately 10-15% of breast cancers lack expression of ERÎI, its target gene progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and are known as triple negative breast cancers (TNBCs). Based on in vitro and clinical data, it is hypothesized that ERÎø could be targeted with selective ligands to inhibit the growth of TNBCs. In order to identify and characterize subtype selective ligands in breast cancer cells, two isogenic reporter cell lines with inducible ERÎI or ERÎø expression and a stably integrated estrogen responsive luciferase reporter were developed. These cell lines were highly sensitive to estrogenic ligands and could be used to characterize known subtype selective ligands. In order to assess the effects of ERÎø expression and ligand treatment on the growth of TNBC cells in vitro and in vivo, the tumorigenic triple negative MDA-MB-468 cell line was engineered with inducible expression of full length ERÎø. These cells were then used to assess growth effects and globally identify the ligand dependent and independent ERÎø target genes using RNA sequencing. In order to specifically detect full length ERÎø in ERÎI negative breast cancers, MDA-MB-468-ERÎø xenograft tumor tissues were used to optimize immunohistochemical protocols for detecting full length ERÎø in breast cancer tissues. The expression of full length ERÎø was then confirmed in a subset of ERÎI/PR/HER2 negative breast cancers using a cohort of triple negative breast cancers. This comprehensive study provides tools to identify subtype selective ligands and detect ERÎø expression in clinical samples, confirms the expression of full length ERÎø in a subset of TNBCs, demonstrates the growth inhibitory effects of ERÎø expression and activation in vitro and in vivo, and globally identifies ERÎø target genes in the context of triple negative breast cancer cells. The results ultimately provide a foundation on which to further develop ERÎø selective ligands with the aim of inhibiting the growth of triple negative, ERÎø-positive breast cancers.

Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer

Author : R P Gayani Kumudu Rajapaksa
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (12 download)

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Book Synopsis Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer by : R P Gayani Kumudu Rajapaksa

Download or read book Understanding the Tumor Repressive Function of Estrogen Receptor Beta in Breast Cancer written by R P Gayani Kumudu Rajapaksa and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Estrogen Receptors in Human Breast Cancer

Author : William L. McGuire
Publisher :
ISBN 13 :
Total Pages : 308 pages
Book Rating : 4.:/5 (49 download)

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Book Synopsis Estrogen Receptors in Human Breast Cancer by : William L. McGuire

Download or read book Estrogen Receptors in Human Breast Cancer written by William L. McGuire and published by . This book was released on 1975 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Orphan Nuclear Receptor Estrogen-Related Receptor Beta in Triple-Negative Breast Cancer

Author : Aileen I Fernandez
Publisher :
ISBN 13 :
Total Pages : 238 pages
Book Rating : 4.:/5 (113 download)

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Book Synopsis The Orphan Nuclear Receptor Estrogen-Related Receptor Beta in Triple-Negative Breast Cancer by : Aileen I Fernandez

Download or read book The Orphan Nuclear Receptor Estrogen-Related Receptor Beta in Triple-Negative Breast Cancer written by Aileen I Fernandez and published by . This book was released on 2019 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Role of Androgen Receptor in Triple-negative Breast Cancer

Author : Valerie N. Barton
Publisher :
ISBN 13 :
Total Pages : 105 pages
Book Rating : 4.:/5 (956 download)

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Book Synopsis The Role of Androgen Receptor in Triple-negative Breast Cancer by : Valerie N. Barton

Download or read book The Role of Androgen Receptor in Triple-negative Breast Cancer written by Valerie N. Barton and published by . This book was released on 2016 with total page 105 pages. Available in PDF, EPUB and Kindle. Book excerpt: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) amplification. Thus, TNBC does not respond to traditional endocrine or HER2-targeted therapies, has a poor prognosis, and lacks effective targeted therapies. Some TNBC tumors express androgen receptor (AR) and may benefit from AR targeted therapies. However, the function of AR in TNBC and efficacy of new generation AR inhibitors are unknown. I hypothesized that AR supports proliferation, metastatic potential, and cancer stem-like cell (CSC) maintenance and that inhibition of AR will decrease tumor burden in preclinical models of breast cancer. My work demonstrates that AR exhibits nuclear expression in at least 22% of primary TNBC tumors. While AR is most abundant in the “luminal AR” (LAR) subtype, non-LAR molecular subtypes are also critically dependent on AR protein. Indeed, AR inhibition significantly reduces baseline proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis in non-LAR molecular subtypes. In vivo, the AR antagonist Enzalutamide (Enza) significantly decreases viability of non-LAR xenografts. Furthermore, AR regulates amphiregulin, which partially rescues the effects of AR inhibition on proliferation, migration, and invasion. AR transcript, protein, and transcriptional activity increase in tumors cells in suspension culture compared to attached conditions suggesting that AR may also maintain CSCs. Indeed, AR inhibition decreases CSCs in vitro. In vivo, pre-treatment with Enza decreases the tumor-initiating capacity of TNBC cells in a limiting dilution assay. Breast CSCs are enriched following chemotherapy and may repopulate the tumor. Indeed, Enza significantly decreases tumor burden when administered during or after chemotherapy in vivo. In summary, AR supports proliferation, metastatic phenotypes, tumor initiating capacity and maintenance of CSCs. AR targeted therapies may represent the first effective targeted therapy for TNBC and greatly improve patient outcomes.

Hormone Receptors in Breast Cancer

Author : Suzanne A. W. Fuqua
Publisher : Springer Science & Business Media
ISBN 13 : 0387094636
Total Pages : 289 pages
Book Rating : 4.3/5 (87 download)

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Book Synopsis Hormone Receptors in Breast Cancer by : Suzanne A. W. Fuqua

Download or read book Hormone Receptors in Breast Cancer written by Suzanne A. W. Fuqua and published by Springer Science & Business Media. This book was released on 2008-12-10 with total page 289 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hormone Receptors in Breast Cancer provides an up-to-date resource of the role of hormone receptors in breast cancer written in depth for both the basic molecular academic researcher and translational scientist. Advances in basic science of molecular endocrinology have undoubtedly been translated into clinical practice, and clinicians caring for this disease need to be knowledgeable about these developments. The molecular basis of hormone action has been elucidated, and the relative significance of the different estrogen and progesterone receptor isoforms has been explored. This explosion of information has lead to exciting new areas of gene specific targeting of the disease, and breast cancer prevention. Paradigm shifts in treatment options and sequencing have recently occurred in breast cancer management, necessitating close cooperation and communication between translational scientists and physicians. This book is focused on providing this communication.

Dissecting the Role of Estrogen Receptor Palmitoylation in Breast Cancer Cells

Author :
Publisher :
ISBN 13 :
Total Pages : 320 pages
Book Rating : 4.:/5 (914 download)

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Book Synopsis Dissecting the Role of Estrogen Receptor Palmitoylation in Breast Cancer Cells by :

Download or read book Dissecting the Role of Estrogen Receptor Palmitoylation in Breast Cancer Cells written by and published by . This book was released on 2013 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen signaling is primarily mediated by two estrogen receptors (ERs), ER[alpha] and ER[beta]. ER[alpha] is expressed in ~70% of breast cancers and is an important diagnostic and therapeutic target. Developing better treatment options and overcoming limitations of endocrine therapy depend on a detailed understanding of ER[alpha]-signaling pathways. ER[alpha], a member of the class I nuclear receptor superfamily of transcription factors, localizes mainly to the nucleus and interacts with DNA regulatory sequences either directly or through interaction with other transcription factors to regulate gene transcription. ER[alpha] is also rapidly activates signaling cascades. S-palmitoylation, a reversible lipid modification is catalyzed by palmitoyl acyl-transferases (PAT), which increase affinity of proteins to the membrane. Based on the results of previous studies, it is hypothesized that palmitoylation of ER[alpha] regulates extranuclear and nuclear signaling of ER[alpha]. We utilized palmitoylation-defective mutant ER[alpha]C447A-expressing MDA-MB-468 breast cancer cells to dissect the role of palmitoylation in a breast cancer cell line model. The substitution of ER[alpha] palmitoylation site abrogated ER[alpha] palmitoylation, membrane localization and estrogen-dependent phosphorylation of ERK1/2 in MDA-MB-468 cell line. Besides loss of E2-dependent extranuclear signaling, the substitution of palmitoylation sites led to the loss of other ER[alpha]-dependent events in ER[alpha]C447A-expressing MDA-MB-468 cells, such as decreased E2-dependent S118 phosphorylation, impaired regulation of certain target genes, and loss of estrogen-dependent cell cycle inhibition. This study thus highlights the importance of ER[alpha] palmitoylation in both nuclear and extranuclear ER signaling pathways in breast cancer cells. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors.

Estrogens, Estrogen Receptor and Breast Cancer

Author : Fritz F. Parl
Publisher : IOS Press
ISBN 13 : 9780967335544
Total Pages : 280 pages
Book Rating : 4.3/5 (355 download)

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Book Synopsis Estrogens, Estrogen Receptor and Breast Cancer by : Fritz F. Parl

Download or read book Estrogens, Estrogen Receptor and Breast Cancer written by Fritz F. Parl and published by IOS Press. This book was released on 2000 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogens have been implicated to play a role in the development of breast cancer. The purpose of this book is to provide a comprehensive analysis of experimental, clinical and epidemiological evidence in support of the carcinogenicity of estrogens.

Epithelial-Mesenchymal Plasticity in Cancer Metastasis

Author : Mohit Kumar Jolly
Publisher : MDPI
ISBN 13 : 3039367242
Total Pages : 512 pages
Book Rating : 4.0/5 (393 download)

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Book Synopsis Epithelial-Mesenchymal Plasticity in Cancer Metastasis by : Mohit Kumar Jolly

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.

Improving Racial and Ethnic Data on Health

Author : National Research Council
Publisher : National Academies Press
ISBN 13 : 0309182573
Total Pages : 58 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Improving Racial and Ethnic Data on Health by : National Research Council

Download or read book Improving Racial and Ethnic Data on Health written by National Research Council and published by National Academies Press. This book was released on 2003-10-15 with total page 58 pages. Available in PDF, EPUB and Kindle. Book excerpt: The panel convened the Workshop on Improving Racial and Ethnic Data in Health to review information about current private-sector and state data collection practices in light of existing federal, state, and local regulations, laws, and requirements. The workshop presentations featured the perspectives of data users, health care providers, insurance plan representatives, state and local public health officials, and regulatory officials. Participants assessed policies, practices, barriers, and opportunities for collecting racial and ethnic data in their settings, and explored ways that private and state systems can be improved to address data needs. In preparation for the workshop, the panel commissioned four background papers to fill gaps in knowledge of private-sector and state government policies and practices and to address the importance of racial and ethnic data collection. The panel is also examining the role of socioeconomic status regarding health and health care disparities. However, the workshop intended to focus only on racial and ethnic data collection. The panel's final report will contain a full consideration of the collection of racial, ethnic, and socioeconomic status data.

Breast Cancer Associated Estrogen Receptors: Catechol Estrogen Receptors in ER-Minus Mice

Author : Dennis Lubahn
Publisher :
ISBN 13 :
Total Pages : 28 pages
Book Rating : 4.:/5 (453 download)

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Book Synopsis Breast Cancer Associated Estrogen Receptors: Catechol Estrogen Receptors in ER-Minus Mice by : Dennis Lubahn

Download or read book Breast Cancer Associated Estrogen Receptors: Catechol Estrogen Receptors in ER-Minus Mice written by Dennis Lubahn and published by . This book was released on 1998 with total page 28 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our research will lead to a better understanding of the developmental, physiological, and biochemical roles of endogenous and environmental estrogens in breast cancer causation, prognosis and treatment. We have found in ER-alpha minus mice a uterine lactoferrin mRNA response to the catechol estrogen, 4-hydroxyestradiol, but not to estradiol. We hynothesize that the putative 4-hydroxyestradiol receptor will elicit additional responses distinct from estradiol and the classic ER-alpha and ER-Beta proteins.

An Investigation of Estrogen Receptor-beta and Its Significance in Human Breast Cancer

Author : Paul J. Balfe
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (81 download)

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Book Synopsis An Investigation of Estrogen Receptor-beta and Its Significance in Human Breast Cancer by : Paul J. Balfe

Download or read book An Investigation of Estrogen Receptor-beta and Its Significance in Human Breast Cancer written by Paul J. Balfe and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Regulation of Estrogen Receptor-alpha Mediated Gene Expression and Endocrine Resistance Through Estrogen Receptor-alpha Phosphorylation and Micro-RNA in Breast Cancer

Download Regulation of Estrogen Receptor-alpha Mediated Gene Expression and Endocrine Resistance Through Estrogen Receptor-alpha Phosphorylation and Micro-RNA in Breast Cancer PDF Online Free

Author : Kyuri Kim
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (774 download)

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Book Synopsis Regulation of Estrogen Receptor-alpha Mediated Gene Expression and Endocrine Resistance Through Estrogen Receptor-alpha Phosphorylation and Micro-RNA in Breast Cancer by : Kyuri Kim

Download or read book Regulation of Estrogen Receptor-alpha Mediated Gene Expression and Endocrine Resistance Through Estrogen Receptor-alpha Phosphorylation and Micro-RNA in Breast Cancer written by Kyuri Kim and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogens are associated with the development and progression of breast cancer in addition to their role in normal reproductive physiology, and estrogen receptors (ER) mediate the actions of estrogen in target tissues by regulating the expression of numerous biologically important target genes. The progression of human breast cancer and the development of resistance to endocrine therapies are thought to be associated with ER phosphorylation. We generated multiple combinations of ER phospho-mutants, at residues serine 104, 106, 118, 167, 236, and 305, and examined their impact on receptor half-life, the agonist and antagonist balance of selective estrogen receptor modulators (SERMs) and selective estrogen receptor downregulators (SERDs), the regulation of ER transcriptional activity, and stimulation of cell proliferation in response to estradiol and SERMs/SERD. We showed that changes in ER affecting the phosphorylation status of the receptor greatly impact receptor function and differential SERM and SERD modulated cellular responses that could contribute to resistance to endocrine therapies in breast cancer. We also studied the regulation of microRNAs (miRNAs) by estradiol and growth factors through ER and extracellular signal-regulated kinase 2 (ERK2) in order to understand their physiological impact on breast cancer. We identified nine miRNA- encoding genes harboring overlapping ER and ERK2 binding sites close to their transcription start sites, which require ER and ERK2 for transcriptional induction as well as estradiol- mediated miRNA regulation. We then identified TP63, a target of miR-101, miR-190 and miR- 196a2, and showed that TP63 plays an important role in estradiol- or growth factor-mediated cellular response in breast cancer cells (MCF-7 and MDA-MB-231) by increasing tumor cell growth and in vitro invasion mainly controlled by miR-196a2 action. These results suggest a tumor-suppressive role of miR-196a2 in regulating TP63 expression and the aggressive behavior of breast cancers.

Biomarkers in Breast Cancer

Author : Giampietro Gasparini
Publisher : Springer Science & Business Media
ISBN 13 : 159259915X
Total Pages : 335 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Biomarkers in Breast Cancer by : Giampietro Gasparini

Download or read book Biomarkers in Breast Cancer written by Giampietro Gasparini and published by Springer Science & Business Media. This book was released on 2008-01-17 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.

The Prognostic Significance of Estrogen Receptor Beta, and Its Isoforms and Correlation with Other Biological Markers in Breast Cancer

Download The Prognostic Significance of Estrogen Receptor Beta, and Its Isoforms and Correlation with Other Biological Markers in Breast Cancer PDF Online Free

Author : Mark Bernard Peter
Publisher :
ISBN 13 :
Total Pages : 428 pages
Book Rating : 4.:/5 (847 download)

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Book Synopsis The Prognostic Significance of Estrogen Receptor Beta, and Its Isoforms and Correlation with Other Biological Markers in Breast Cancer by : Mark Bernard Peter

Download or read book The Prognostic Significance of Estrogen Receptor Beta, and Its Isoforms and Correlation with Other Biological Markers in Breast Cancer written by Mark Bernard Peter and published by . This book was released on 2010 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt:

The Role of Estrogen Receptor Alpha in Tumorigenic Breast Cancer Cells

Author :
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (946 download)

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Book Synopsis The Role of Estrogen Receptor Alpha in Tumorigenic Breast Cancer Cells by :

Download or read book The Role of Estrogen Receptor Alpha in Tumorigenic Breast Cancer Cells written by and published by . This book was released on 2004 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen receptor alpha (ER alpha) is the most common target of treatment in human breast cancer. The expression of ER alpha has long been known as a positive prognostic indicator. While human breast cancers are composed of heterogeneous populations of cells, previous studies of ER alpha expression and function have focused on bulk tumor cells. With the recent discovery that breast cancer growth is driven-by a tumorigenic subpopulation of cancer cells, it has become vital to study the role of ER alpha in this population of cells.

Role of Estrogen Receptor Variants in Tumorgenesis of Human Breast Cancer

Author :
Publisher :
ISBN 13 :
Total Pages : 394 pages
Book Rating : 4.:/5 (227 download)

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Book Synopsis Role of Estrogen Receptor Variants in Tumorgenesis of Human Breast Cancer by :

Download or read book Role of Estrogen Receptor Variants in Tumorgenesis of Human Breast Cancer written by and published by . This book was released on 1999 with total page 394 pages. Available in PDF, EPUB and Kindle. Book excerpt: In order to determine whether differences exist in expression of estrogen receptor (ER) variant mRNAs between normal and tumor breast tissues, we have analyzed by reverse transcription-polymerase chain reaction (RT-PCR) ER variants mRNA expression in matched normal breast tissue and breast tumor components. A higher expression of exon 5-deleted, and of ERC4 variants in the tumor component compared to the normal counterpart of matched samples was seen whereas a higher expression of exon 3-deleted ER variant in the normal tissue was observed. This is consistent with previous observations made on independent samples. We have described the presence within normal breast as well as in breast tumor tissues of several variant forms of ER-beta mRNA deleted in exon 5, exon 6, exon 5+6 or exon 8 sequences. The balance between some of these different ER-beta isoforms was modified during breast tumorigenesis and tumor progression. We also showed that a higher ER-alpha/ER-beta ratio was observed in the breast tumors compared with their matched normal breast tissues. This increase was attributed to an increase in ER-alpha mRNA expression and a lower ER-beta mRNA expression in the tumor compared with that of the normal component in some ER+ cases.