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Author: Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
This project addresses three fundamental research issues. The first question is whether or not molecular lesions of the genes involved in the TGFB signaling pathway contribute to the origin and/or progression of breast cancer. We expect changes in these genes to be relatively late events, perhaps characteristic of metastatic cancer. Secondly, we propose to determine how molecular lesions in the TGFB receptor and/or Smad genes affect receptor function, and how they might play a role in the development and/or progression of breast cancer. Thirdly, we intend to examine the question whether genetic lesions in TGFB receptor and/or Smad genes are able to predict the outcome of patients with breast cancer. Because the anti-tumor effects of anti-estrogens such as tamoxifen are thought to be mediated by the auto-and paracrine induction of TGFB, we wish to test the hypothesis that resistance of hormone-receptor positive cancers to tamoxifen is the result of inactivation of TGFB pathway genes.
Author: Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
This project addresses three fundamental research issues. The first question is whether or not molecular lesions of the genes involved in the TGFB signaling pathway contribute to the origin and/or progression of breast cancer. We expect changes in these genes to be relatively late events, perhaps characteristic of metastatic cancer. Secondly, we propose to determine how molecular lesions in the TGFB receptor and/or Smad genes affect receptor function, and how they might play a role in the development and/or progression of breast cancer. Thirdly, we intend to examine the question whether genetic lesions in TGFB receptor and/or Smad genes are able to predict the outcome of patients with breast cancer. Because the anti-tumor effects of anti-estrogens such as tamoxifen are thought to be mediated by the auto-and paracrine induction of TGFB, we wish to test the hypothesis that resistance of hormone-receptor positive cancers to tamoxifen is the result of inactivation of TGFB pathway genes.
Author: Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
This project addresses the question whether and, if so, how molecular lesions of the genes involved in the TGFB signaling pathway contribute to the origin and/or progression of breast cancer. We have cloned and determined the intron-exon structure of the TGFB type I receptor (TBR-I). This has allowed us to study this gene in a series of primary breast cancer specimens. Our most important finding is a much higher frequency of an exon 1 receptor variant among breast cancer cases than controls. Secondly, we have identified a serine to tyrosine mutation within the catalytic core of the TBR-I serine-threonine kinase domain in 2 of 31 primary and 5 of 12 metastatic breast cancer specimens. Thirdly, we have developed transient transfection as says to determine how specific TBR mutations affect receptor function. Using these assays we have shown that two previously identified TBR-II missense mutants are incapable of signaling because of the near complete loss of receptor kinase activity. Plans for the coming year include completing structural analyses of the TBR-I and -II genes in primary and metastatic breast cancer and defining the functional properties of the newly discovered TBR-I variant and mutant.
Author: Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
Transforming Growth Factor-Beta (TGF-Beta) is the most potent known inhibitor of cell cycle progression of normal mammary epithelial cells. In general, advanced breast cancers are refractory to TGF-Beta-mediated growth inhibition. The TGF-Beta type I and type II receptors (T-Beta-R-I and -II) are the primary transducers of TGF-Beta's antiproliferative effects. It is our working hypothesis that TGF-Beta-resistance is caused by lesions in the T-Beta-R genes. Using touch preps of primary breast carcinomas, we showed that approximately 50% of primary breast carcinomas contain subpopulations of cells that have lost one or both copies of the T-Beta-R-I or -II gene. Screening of the T-Beta-R-I and -II genes for the presence of mutations using PCR-SSCP and DNA sequencing indicate that a particular missense mutation (S387Y) in T-Beta-R-I is present in approximately 6% of primary cancers and 42% of axillary lymph node metastases. Finally, we have generated antibodies that specifically recognize the activated (phosphorylated) forms of Smad2 and -3. These allow us to assess in situ whether breast cancer cells are responding to TGF-Beta, and whether T-Beta-R defects are present or not. Approximately 12% of primary breast cancers fail to activate Smad2, indicating the presence of a TGF-Beta receptor defect.
Author: Sonia B. Jakowlew Publisher: Springer Science & Business Media ISBN: 1597452939 Category : Medical Languages : en Pages : 785
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: 1588297144 Category : Medical Languages : en Pages : 726
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: Wen G. Jiang Publisher: Springer Science & Business Media ISBN: 0306483998 Category : Medical Languages : en Pages : 310
Book Description
about the involvement of signaling Transforming growth factor in tumor development and metastasis. plays a central role in the signaling network that controls morphogenesis, 2. THE BASICS OF growth and cell differentiation in SIGNALING multicellular organisms. The different members of this pleiotropic family of 2. 1. receptor signaling growth and differentiation factors seem to The family of growth factors regulate many processes in human disease consists of more than thirty members in and, in particular, tumor development. humans alone (15, 16). They cluster in Our understanding of how two major groups, the group composed of initiated signals are mediated has both the bone morphogenetic proteins increased dramatically in the last fifteen (BMP) and growth and differentiation years. Firstly, the prototype of factors (GDFs), and the group formed by this still constantly growing family, was the Activins, and Nodals. The two identified and cloned (1). Secondly, the groups differ in their use of receptors for family receptors were transmembrane receptors and the identified by expression cloning from subsequent activation of the mammalian tissue culture (2-7). Thirdly, transcriptional mediators (for recent genetic screens in Drosophila reviews see (13, 14, 17)).
Author: Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
The overall goal of this research is to understand the importance of the interaction between Smad3 and the estrogen receptor (ER) as it pertains to human breast tumorigenesis and breast cancer progression. Preliminary data from our laboratory had suggested that ERalpha, ERbeta1, ERbeta2 and ERbeta5 interact with Smad3 in the yeast two-hybrid system. Our current data suggests that a weak interaction between ERalpha and ERbeta1 with Smad3 exists in vitro but not in vivo. Furthermore, although Smad3 does not affect ER transcriptional activity on a vitellogenin ERE, both ERalpha and ERbeta1 inhibit Smad3 transcriptional activity on the p3TP-Lux reporter in Cos1 cells. However, the ERbeta variants, ERbeta2 and ERbeta5 did not affect Smad3 transcription. We are currently in the process of confirming these results in a human breast cancer cell line. Overall, the data support the hypothesis that ER interacts with the TGFbeta signal transduction pathway. The possible mechanisms by which ER affects Smad3 transcription are being investigated.
Author: Aristidis Moustakas Publisher: Springer Science & Business Media ISBN: 4431544097 Category : Science Languages : en Pages : 463
Book Description
Transforming growth factor-β (TGF-β) is a secreted polypeptide with multifunctional properties manifested during embryonic development, adult organ physiology, and pathobiology of major diseases, including cancer and fibrotic and cardiovascular diseases. The signaling pathway of TGF-β now is rather well understood. Continuing revelations in the mechanisms of action of TGF-β provide specific mechanistic examples of how human cells lose their controlled function and behave wrongly during the development of diverse diseases. Equally important, however, is the current promise of exploiting the TGF-β pathway in combating human disease. This book comprehensively covers major areas of human disease where the involvement of TGF-β is firmly established. Simultaneously, the book highlights major gaps in knowledge and the future directions of research that can benefit human medical science. The core set of diseases where TGF-β action is well documented and are included in the book are cancer and cardiovascular and fibrotic disorders. The central aim of the book is to stimulate young scientists to enter the prolific TGF-β field and find new solutions to the problems remaining in this area of study. For this purpose the book provides authoritative educational chapters that furnish a good introduction to the field for young doctoral students, postdocs, and clinical fellows. The book also serves as a valuable reference for the aficionados in the field, who can find accessible and well-illustrated material for their teaching and lecturing activities, via which the importance of TGF-β biology is disseminated to the world of science and to the public.
Author: Robert C. Bast, Jr. Publisher: John Wiley & Sons ISBN: 111900084X Category : Medical Languages : en Pages : 2004
Book Description
Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
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Author: Sonia B. Jakowlew
Author: Sonia B. Jakowlew
Author: Jacqueline C. Newby
Author: Wen G. Jiang
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Author: Aristidis Moustakas
Author: Robert C. Bast, Jr.