Analysis of the Regulation of Expression of Transforming Growth Factor-Beta in Human Breast Cancer Cells PDF Download

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Languages : en
Pages : 26

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This combined final report for the research and career development grants relates to three objectives. Work on the first objective first focused on an analysis of the importance of TGF-beta expression as a determinant of clinical outcome. No such correlation was evident. Subsequent experiments examined the importance of a functionally intact TGF-beta signaling pathway with regards to tumor necrosis factor (TNF)-mediated cytotoxicity of MCF-7 cells, and documented that derepression of Bcl-2 expression as a consequence of loss of TGF-beta responsiveness likely underlies the acquired resistance to TNF. The second objective centered around an in vivo model of tumorigenicity and metastatic potential of breast cancer cells altered with regard to their production of and responsiveness to TGF-beta. Distinct paracrine and autocrine roles for TGF-beta were highlighted, with local invasiveness determined to be largely a paracrine effect of TGF-beta. The most rapid tumor growth was evident with the cells that remained responsive to TGF-beta however. The third onjective was to identify the molecular determinants of promoter usage for TCF-beta3 in breast cancer cell lines. Hypomethylation at a small grouping of CpGs in breast cancer cells was identified as a molecular correlate of downstream promoter activation.

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Languages : en
Pages : 0

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The primary focus of the research is the expression of TGF-Beta by breast cancer cells. For established tumors, overexpression of TGF-Beta may result in increased in vivo tumor growth and metastatic spread. The first objective involves the analysis of resected breast cancer specimens, with the goal of confirming our prior work correlating clinical outcome with TGF-Beta expression levels in tumors. There are as yet no definitive data or conclusions from this aspect of the work. The second objective of the grant was to evaluate the impact of TGF-Beta on the tumorigenic and metastatic potential of human breast cancer cell lines in nude mice. We have made progress on generating the transfected cell clones, but do not yet have data regarding animal studies. The third research objective is the analysis of the regulation of TGF-Beta expression in breast cancer cells.

Author: Sonia B. Jakowlew
Publisher: Springer Science & Business Media
ISBN: 1588297144
Category : Medical
Languages : en
Pages : 726

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Book Description
Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The first volume, Basic and Clinical Biology, is divided into three parts. This volume’s companion, Cancer Treatment in Therapy, examines transforming growth factor- ß in other developing and advanced cancers and methods of treatment and therapy.

Author: Sonia B. Jakowlew
Publisher: Springer Science & Business Media
ISBN: 1597452939
Category : Medical
Languages : en
Pages : 785

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Book Description
Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The second volume, Cancer Treatment in Therapy, is divided into three parts. The companion volume details the role of TGF- ß on basic and clinical biology.

Author: Sonia B. Jakowlew
Publisher: Springer Science & Business Media
ISBN: 1597452920
Category : Medical
Languages : en
Pages : 726

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Book Description
Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The first volume, Basic and Clinical Biology, is divided into three parts. This volume’s companion, Cancer Treatment in Therapy, examines transforming growth factor- ß in other developing and advanced cancers and methods of treatment and therapy.

Author: Nadège Fils - Aimé
Publisher:
ISBN:
Category :
Languages : en
Pages :

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"Transforming growth factor-beta (TGF-beta) plays an important role in breast cancer progression as a pro-metastatic factor, notably through enhancement of cell migration. It is becoming clear that micro-RNAs (miRNAs), a new class of small regulatory molecules, act downstream of TGF-beta at several steps of cancer progression. We report here the down-regulation of miR-584 by TGF-beta in a panel of breast cancer cell lines. We found this regulation to be required for TGF-beta-mediated cell migration. Moreover, we determined that the protein phosphatase and actin regulator 1 (PHACTR1), an actin-binding protein, was positively regulated by TGF-beta and inhibited by miR-584. The presence of PHACTR1 was required for TGF-beta to promote the migration of invasive breast cancer cells. Finally, both the over-expression of miR-584 and the knock-down of PHACTR1 resulted in a major re-organization of the actin cytoskeleton. We thus propose a mechanism whereby TGF-beta silences the expression of miR-584 to enhance this of PHACTR1, resulting in a re-arrangement of actin that leads to promotion of breast cancer cell migration." --

Author: Jimin Guo
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Languages : en
Pages :

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"A canonical Transforming Growth Factor Beta (TGF[beta]) signalling pathway, mediated through Smad2, Smad3 and Smad4 proteins, plays context-dependent roles in mammary tumorigenesis and breast cancer progression. These roles vary from maintaining mammary tissue homeostasis to promoting breast cancer metastasis. In the studies presented in this thesis, my colleagues and I take both a computational approach and an experimental approach to address the implications of TGF[beta]-Smad signalling in human breast cancer and its cross talk with Angiotensin II pathway. Our computational study results in a Decision Tree classification model that uses standardized immunohistochemistry (IHC) scores and breast cancer disease characteristics to predict whether a patient will develop early breast cancer relapse. It reveals pathological nodal status, stroma percentage in tumor core and percentages of tumor cells expressing TGF[beta]/Smad signalling components as determinant factors for early breast cancer relapse prediction. Our experimental study identifies a novel positive feedback mechanism downstream of TGF[beta] in breast cancer cells, mediated through Breast Cancer Anti-Estrogen Resistance 3 (BCAR3). We show that BCAR3 inhibits the TGF[beta]/Smad signalling pathway and biological responses to TGF[beta] in breast cancer cells. TGF[beta], in term, down regulates endogenous BCAR3 protein level to mediate a positive feedback loop. In parallel to these studies, we also further characterize a previously identified signalling mechanism in our laboratory, namely TGF[beta]-induced expression of G protein coupled receptor kinase 2 (GRK2). We show that TGF[beta] antagonizes Angiotensin II (Ang II)-induced mitogen-activated protein kinase (MAPK) activation in vascular smooth muscle cells. Altogether, our studies extend the current knowledge on the TGF[beta]-Smad signalling in 3 dimensions: its prognostic value in breast cancer, its intracellular regulation and its crosstalk with other signalling pathway." --

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Publisher: ScholarlyEditions
ISBN: 1464935211
Category : Science
Languages : en
Pages : 69

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Book Description
Advances in Transforming Growth Factor beta Research and Application: 2011 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Transforming Growth Factor beta in a concise format. The editors have built Advances in Transforming Growth Factor beta Research and Application: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Transforming Growth Factor beta in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Advances in Transforming Growth Factor beta Research and Application: 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.

Author: Michael B. Sporn
Publisher: Springer Science & Business Media
ISBN: 3642773834
Category : Medical
Languages : en
Pages : 177

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It is now apparent that several fields of investigation are converging upon each other as the goal of finding a practical way to prevent cancer is pursued. The present monograph represents the efforts of an interdisciplinary ESO Task Force that was convened to assess interactions of peptide growth factors and steroid-like molecules in the prevention of cancer. Each of the participants in the Task Force represents a differentscientific discipline, and the monogrph is intended to be a synthesis of their different approaches to the common problem of cancer prevention. It is hoped that the reader will find this monograph to be of use in the evaluation of both preclinical and clinical approaches to the major issues that face us in chemoprevention. It is clear that prevention of cancer is an idea whose time has come, and the problem now is to implement the most effective approaches toward achieving the desired goals.

Author: Jose Russo
Publisher: Springer Science & Business Media
ISBN: 1461448840
Category : Medical
Languages : en
Pages : 461

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Book Description
This book will provide the latest advances in molecular and cellular biology for establishing the foundation of a complete understanding of the mechanisms of breast differentiation leading to cancer prevention. The authors are based on the epidemiological evidence indicating that early first full term pregnancy is a protective factor in human against breast cancer and they have used this paradigm and developed experimental systems in both in vivo and in vitro that have demonstrated mechanistically how the differentiation at the organ and cellular level takes place. This knowledge has provided the blueprint for developing better understanding of the basis of cancer prevention. The transcriptoma analysis of the breast of pre and post-menopausal women has established a genomic signature imprinted in the breast that differs according to the reproductive history of the woman showing that early first full term pregnancy reprogram the organ. This reprogramming takes place at the chromatin level by changing the transcriptional process. The modification of the transcriptional control is due to the expression of non coding RNA sequences and posttranscriptional control driven by the splicesome. The plasticity of the genome of the human breast make possible this reprogramming that is not only induced by the physiological process of pregnancy but by the use of hormones that mimic pregnancy without pregnancy. The author have established the basis of clinical trials for prevention and the discovery that short 15aa peptides of the chorionic gonadotropin hormone can be used in human breast cancer prevention based on preclinical and clinical data.