The Effect of TGF Beta1 on the Proliferation and Differentiation of Normal Rat Mammary Epithelial Cells PDF Download
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Author: Xiaoyuan Zhao
Publisher:
ISBN:
Category :
Languages : en
Pages : 170
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Book Description
Author: Xiaoyuan Zhao
Publisher:
ISBN:
Category :
Languages : en
Pages : 170
Get Book Here
Book Description
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 25
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Book Description
We report that MMTV-DNIIR female mice have accelerated mammary gland differentiation during early pregnancy with impaired development during late pregnancy and lactation followed by delayed post-lactational involution. Mammary tumors, mostly carcinoma in situ, developed spontaneously in the MMTV-DNIIR mice with a long median latency (27.5 months). Invading carcinoma cells in MMTV-DNIIR animals showed loss of DNIIR transgene expression as determined by in situ hybridization. The data indicate that signaling from endogenous TGF-Betas not only plays an important role in normal mammary gland physiology but also can also suppress the early stage of tumor formation and contribute to tumor invasion once carcinomas have developed. The ability of the TGF-beta signaling pathways to inhibit proliferation of many epithelial cells while stimulating proliferation fibroblasts remains a conundrum. We found that the absence of RhoA and p160(ROCK) activity in fibroblastic NIH3T3 cells and its presence in mammary epithelial NMuMG cells can at least partially explain the difference in the TGF-beta growth response. TGF-beta stimulation of pl60(ROCK)-mediated inactivation of the cdk-activating phosphatase, cdc25A, blocks G1-S progression in NMuMG cells. These results provide novel evidence that TGF-beta signaling through RhoA and pl60(ROCK) links signaling components for epithelial transdifferentiation with regulation of cell cycle progression.
Author: Gregory R. Bock
Publisher: John Wiley & Sons
ISBN: 0470514078
Category : Science
Languages : en
Pages : 264
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Book Description
TGF-beta, originally identified as a transforming growth factor with similar properties, is now known to exist as a family of factors with similar properties. These factors promote cell proliferation in some tissue types or conditions and induce cell differentiation in others. Features the latest information on the TGF-beta family and its receptors. Describes correlations between TGF-beta and certain cancers, including glioblastomas. Also contains reports of preliminary investigations of clinical applications for TGF-beta in many diseases, including leukemia and its use to accelerate wound healing.
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Category :
Languages : en
Pages : 0
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The pleiotropic cytokine tumor necrosis factor-alpha (TNF) has previously been shown to regulate both the proliferation and differentiation of normal rat mammary epithelial cells (MEC) in primary culture. TNF and TNF receptor expression were measured in isolated MEC and found to be independently and specifically regulated during mammary gland development. Using agonistic antibodies to either TNF receptor, the individual roles of each receptor were investigated in MEC in primary culture. The p55 TNF receptor was found to be the sole mediator of TNF-induced proliferation, while the two receptors were found to have opposing effects on functional differentiation. Further studies were undertaken to determine whether the post-receptor pathway of TNF action in MEC involved subsequent signaling via the EGF receptor. Using an inhibitor of the EGF receptor tyrosine kinase activity, PD158780, it was determined that the EGF receptor is not necessary for TNF action in normal MEC. Lastly, TNF and TNF receptor expression were measured in both DMBA- and NMU-induced mammary tumors, and the effects of TNF on the growth and morphogenesis and NMU-initiated and -transformed MEC in culture were determined.
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Category :
Languages : en
Pages :
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Transforming growth factor [beta]1 (TGF[beta]1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor [alpha] (ER[alpha]) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF[beta]1 is necessary for the quiescence of ER[alpha]-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF[beta]1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF[beta] signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER[alpha]. To test whether TGF[beta] was functional, we examined genetically engineered mice with different levels of TGF[beta]1. ER[alpha] co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf[beta]1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF[beta]1 via the MMTV promoter suppressed proliferation of ER[alpha] positive cells. Thus, TGF[beta]1 activation functionally restrains ER[alpha] positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF[beta]1 dysregulation may promote proliferation of ER[alpha] positive cells associated with breast cancer risk in humans.
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Category :
Languages : en
Pages : 32
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Transforming growth factor beta 1 (TGF-beta 1) orchestrates the response of different cell types to injury via regulation of proliferation, apoptosis and ECM composition. Previously we discovered that TGF beta 1 is rapidly activated in mammary gland following radiation. Because TGF- beta 1 is implicated in regulation of proliferation and apoptosis, we investigated whether the activation of TGF-beta 1 contributes to the cell fate decisions in response to radiation. We found that radiation-induced apoptosis and cycle cell arrest are absent in adult mammary epithelium and embryonic liver and epidermis when TGF-beta 1 is compromised. Since p53 abundance and activity is thought to dictate apoptotic cellular responses to radiation, we examined the p53 response. We found that both chronic and transient depletion of TGF-beta 1 compromise the p53 response. In order to study the mechanism by which TGF-beta 1 affects the p53 response we cultured mammary epithelial cells (MECs). This in vitro model present TGF-beta 1 dependent radiation response similar to that seen in vivo. Treatment of MECs with TGF-beta 1 restored both p53 response and caspase 3 cleavage in the heterozygote cultures. We propose that TGF-beta 1 is a key regulator of epithelial genomic integrity since its loss impairs activation of p53 resulting in reduced apoptosis and cell cycle arrest.
![The TGF-[beta] Family PDF](https://books.google.com/books/content/images/frontcover/QW5xq75p5gYC?fife=w80-h100)
Author: Rik Derynck
Publisher: CSHL Press
ISBN: 0879697520
Category : Transforming growth factors-beta
Languages : en
Pages : 1108
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Book Description
Transforming growth factor-[beta] (TGF-[beta]), identified nearly three decades ago, is a secreted polypeptide that functions in critical cell cycle processes, including cellular proliferation, differentiation, and development: It belongs to a large protein family that, in humans, contains 33 members, including activins, inhibins, bone morphogenetic proteins, growth and differentiation factors, and Mullerian inhibiting substance. This volume draws on the world's leading laboratories to comprehensively cover all aspects of the biology of TGF-[beta] and related factors. In addition to providing historical and background information, it describes the cell biology and signaling pathways of TGF-[beta] members in detail, including the roles of TGF-[beta] factors in the development and physiology of humans and model organisms. The last few chapters are devoted to the role of TGF-[beta] members in cancer and other diseases, as well as the possibilities for therapeutics based on knowledge of signaling pathways and macromolecular structures. It serves as a comprehensive reference work for both specialists and researchers less familiar with the field.
Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1808
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![The Effect of TGF-[beta] and Other Growth Factors on the Growth and Transdifferentiation of Mammary Epithelial Cells PDF](https://books.google.com/books/content/images/frontcover/CE7vNwAACAAJ?fife=w80-h100)
Author: Allison J. Darling
Publisher:
ISBN:
Category : Epithelial cells
Languages : en
Pages : 184
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Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Epidermal growth factor (EGF) and transforming growth factor a (TGFalpha) acting through EGF receptors (EGFR) regulate the development of normal mammary epithelial cells (MEC) and breast cancer. Primary culture studies examined the effects of EGF and TGFalpha in MEC. PD158780, a selective inhibitor of the tyrosine kinase domain of EGFR, helped demonstrate that EGFR signaling was required for the proliferation and functional differentiation of immature MEC from days 0-7 of culture, and survival of terminally differentiated MEC from days 17.5-21 of the study. EGFR levels were expressed at high levels in non-functional MEC and MEC undergoing apoptosis whereas functionally differentiated MEC expressed relatively low levels of EGFR. In EGF medium, cultured MEC expressed peak levels of erbB2 and erbB3 from day 7-14 of culture, whereas erbB4 levels were only detected within MEC cultured for 7 and 10.5 days. MEC isolated from mammary glands expressed high levels of erbB2 and erbB3 in virgin rats and rats during pregnancy and involution, and relatively low levels during lactation, whereas erbB4 appeared to be uniformly expressed throughout the developmental stages analyzed. These findings will help in the development of therapies to treat aggressive human breast cancers that often overexpress EGFR and/or other erbB receptors.
