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Regulated Trafficking And Spatially Restricted Signaling Of The Epidermal Growth Factor Receptor In Human Mammary Epithelial Cells
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Book Synopsis Regulated Trafficking and Spatially Restricted Signaling of the Epidermal Growth Factor Receptor in Human Mammary Epithelial Cells by : Patrick Martin Burke
Download or read book Regulated Trafficking and Spatially Restricted Signaling of the Epidermal Growth Factor Receptor in Human Mammary Epithelial Cells written by Patrick Martin Burke and published by . This book was released on 2000 with total page 364 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Effects of Signaling Through the EGF Receptor System Upon Regulation of Growth in Human Mammary Epithelial Cells by : Becky Worthylake
Download or read book The Effects of Signaling Through the EGF Receptor System Upon Regulation of Growth in Human Mammary Epithelial Cells written by Becky Worthylake and published by . This book was released on 1997 with total page 17 pages. Available in PDF, EPUB and Kindle. Book excerpt: Previous reports showed that transactivation of the human epidermal growth factor receptor 2 (HER2) by epidermal growth factor (EGF) leads to the downregulation of HER2. This report presents evidence that overexpression of HER2 nearly abolished its downregulation. Unexpectedly, downregulation of the epidermal growth factor receptor (EGFR) was also inhibited by overexpression of HER2. This suggests that the EGFR and HER2 share a trafficking component which becomes limiting when HER2 is overexpressed. There are two trafficking steps which kinetic analyses predict to be regulated by a saturable component: internalization and lysosomal targeting. We show that the internalization rate of the EGFR is independent of the level of HER2 expression. Thus, we speculate that the molecule responsible for lysosomal targeting is shared between EGFR and HER2. Further, this implies that overexpression of one of the EGFR family members can cause misregulation of the receptors expressed at normal levels.
Book Synopsis Spatial Distribution of the EGF Receptor in Regulation of Breast Epithelial Cell Growth and Organization by :
Download or read book Spatial Distribution of the EGF Receptor in Regulation of Breast Epithelial Cell Growth and Organization written by and published by . This book was released on 1995 with total page 16 pages. Available in PDF, EPUB and Kindle. Book excerpt: The spatial distribution of the EGF receptor and ligands is necessary for normal organization and proliferation of human mammary epithelial cells. We found that these cells express high levels of EGF receptors. These receptors are rapidly internalized and recycled. Unlike transformed cells, internalization efficiency of normal HMEC is high. These cells also make high levels of EGF, TGF-alpha, HB-EGF and amphiregulin, although TGF-alpha and amphiregulin appear to be the predominant ligands. We transfected cells with a gene encoding an artificial ligand consisting of the mature sequences of EGF (sEGF). Cells expressing sEGF could not be inhibited by antagonistic anti-EGF-R antibodies, apparently because the sEGF was working through an intracrine mechanism. Importantly, cells expressing sEGF could not organize correctly. Also, the ability of HMEC to spread and migrate on the extracellular matrix was dependent of EGF-R occupancy. Our data suggests that the ability to HMEC to spatially sense their environment is dependent on the EGF-R system through an autocrine mechanism. Importantly, these data support our hypothesis that disruptions in the spatial aspects of EGF-R signaling could facilitate the development of breast cancer.
Book Synopsis Spatial Distribution of the EGF Receptor System in the Regulation of Breast Epithelia Cell Growth and Organization by :
Download or read book Spatial Distribution of the EGF Receptor System in the Regulation of Breast Epithelia Cell Growth and Organization written by and published by . This book was released on 1995 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: 184A1 human mammary epithelial cells (HMECs) form organotypic structures when plated on Matrigel. However, the organotypic structures differentiate into squamous, not glandular, epithelia. They can not be used to examine the functional significance of a polarized epidermal growth factor receptor system in a glandular epithelia. This experimental system may be useful for investigating cell-extracellular matrix interactions that control EGF-R expression. 184A1s and subclones of the 184A1 cell line express proteins necessary for structural and functional polarization on Transwells, but do not assemble these proteins into tight junctions. MCF-7 cells express ZO-1 and assemble the protein into tight junctions when plated onto Transwells. MCF-7s also segregate B-1 integrin into the basal-lateral membrane coppartment. NCF-7 cells respond mitogenicly to EGF-R occupancy and may provide an experimental system with which to address the primary aim of my proposal: to determine if the loss of the correct spatial organization or inappropriate expression of the EGF-R system provides a growth advantage, enhances cell motility, or ochanges the differentiated state of normally organized epithelial cells.
Book Synopsis Trafficking Inside Cells by : Nava Segev
Download or read book Trafficking Inside Cells written by Nava Segev and published by Springer Science & Business Media. This book was released on 2010-05-30 with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.
Book Synopsis The Effects of Soluble Epidermal Growth Factor Receptor in Mammary Epithelial Cells by : Jennifer J. Gavinski
Download or read book The Effects of Soluble Epidermal Growth Factor Receptor in Mammary Epithelial Cells written by Jennifer J. Gavinski and published by . This book was released on 2008 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Regulation of ErbB Signaling in Breast Cancer Epithelial Cells by Cb1 Proto-Oncogene Product by :
Download or read book Regulation of ErbB Signaling in Breast Cancer Epithelial Cells by Cb1 Proto-Oncogene Product written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: A large body of evidence has shown that members of the epidermal growth factor (EUF) family play critical roles in the proliferation and differentiation of normal breast epithelial cells and are important for cell proliferation in breast cancer. The response to EGF is mediated by the transmembrane receptor tyrosine ErbB 1, or epidermal growth factor receptor (EGF-R). This receptor plays a key role in the induction of proliferation in mammary epithelial cells (MECs). Overexpression of EGF-R due to gene amplification or increased transcription is seen in a third or more of all breast cancers. Receptor overexpression may be causally linked to oncogenesis, and correlates with development and progression of tumors that are refractile to standard therapeutic approaches. Thus, EGF-R is a potential target for therapeutic intervention in the subset of women with worst prognosis on conventional treatment. Understanding and manipulating the biochemical mechanisms regulating signal transduction through EGF-R therefore represent important goals in breast cancer research, and are the focus of this study. We have proposed the hypothesis that the proto-oncoprotein Cbl provides ligand-specific negative regulation of EGF-R in epithelial cells. We and others have shown that Cbl effects EGF- mediated down-regulation, ubiquitination, and degradation of EOF-R. In the 8.5 months of this reporting period (following reactivation of the award at the place of the P.I.'s independent appointment), we have tested whether Cbl's recruitment to the receptor and its ability to ubiquitinate EGF-R depends on the nature of the stimulating ligand. In vivo, EGF stimulation of EGF-R leads to receptor downregulation and the termination of signaling, but TGF-alpha stimulation of EUF-R leads to receptor recycling and prolonged signaling. We have found that EGF-activated EUF-R binds to Cbl and undergoes polyubiquitination, but TGF-alpha-activated EGF-Rdoes the same.
Book Synopsis Spatial Distribution of the EGF Receptor System in the Regulation of Breast Epithelial Cell Growth and Organization by :
Download or read book Spatial Distribution of the EGF Receptor System in the Regulation of Breast Epithelial Cell Growth and Organization written by and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 184A1 cells do not form polarized, glandular epithelial structures when plated onto Matrigel, nor do they polarize if plated onto Transwell tissue culture inserts; therefore, 184A1 could not be used to address the primary aim of my proposal: to determine if the loss of receptor system polarization provides a growth advantage, enhances motility, or changes the differentiated state of normal cells. However, because the growth and motility of 184A1 cells require EGFR stimulation and because EGFR mis-regulation is implicated in the progression of human breast cancer, the 184A1 cell system still represents a excellent cell system in which to investigate EGFR regulation. My work has revealed that the constitutive endocytosis of the empty EGFR can be an active and specific form of EGFR spatial regulation in 184A1 cells. The process requires formation of coated pits, is specific and saturable for the EGFR and is upregulated at high cell densities. As a result of the rapid constitutive endocytosis, there is a significant increase in the proportion of receptors that can be found within the cell. Mounting evidence suggests that activated receptors initiate different signaling pathways if they are localized to vesicles as opposed to plasma membrane associated. Rapid constitutive endocytosis may provide a mechanism by which a large pool of receptors is made available to initate, preferentially, signals from internal vesicular membranes. Endocytosed ligands, or internalized, pre-activated E6FR or receptor family members could activate the internal pool of receptors either directly or in trans, respectively.
Book Synopsis The Role of Epidermal Growth Factor Receptor in Hepatocyte Growth Factor Signaling in Mammary Epithelial Cells by : Alyssa Rowena Bonine-Summers
Download or read book The Role of Epidermal Growth Factor Receptor in Hepatocyte Growth Factor Signaling in Mammary Epithelial Cells written by Alyssa Rowena Bonine-Summers and published by . This book was released on 2006 with total page 109 pages. Available in PDF, EPUB and Kindle. Book excerpt: Deregulated hepatocyte growth factor (HGF) and c-Met signaling leads to increased tumor cell invasion and growth that is observed in mammary carcinogenesis. Determining the specific role of HGF/c-Met signaling in breast cancer has been compounded by the fact that c-Met communicates with a number other receptor pathways that lead to various pathological outcomes. In the present study we show that the epidermal growth factor receptor (EGFR) plays a direct role in HGF/c-Met mediated biological activities. We used the clinically relevant EGFR inhibitors gefitinib and erlotinib to determine the role of EGFR in mediating HGF signaling. Inhibition of EGFR through these small molecule inhibitors significantly reduces the ability of HGF to induce proliferation, cell motility and invasion as well as cell scattering in various mammary epithelial cells. Furthermore, our data indicate that gefitinib and erlotinib negatively regulate the ability of HGF to activate its cognate receptor c-Met and that this action is EGFR-dependent. Our results provide a novel mechanism of action for EGFR as a mediator of HGF signaling thereby linking EGFR to the oncogenic potential of c-Met in mammary carcinomas cells.
Book Synopsis Growth Hormone (GH) Modulation of Epidermal Growth Factor (EGF) Signalling in Human Mammary Epithelial Cells by : Verena Maria Wölker
Download or read book Growth Hormone (GH) Modulation of Epidermal Growth Factor (EGF) Signalling in Human Mammary Epithelial Cells written by Verena Maria Wölker and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Zusammenfassung: This study demonstrates crosstalk between Growth Hormone (GH) and Epidermal Growth Factor (EGF) in two different breast cancer cell lines. Long-term modification of cell viability and the ERK1/2 and AKT pathways was only detected in MDA-231 cells. By simultaneous treatment with GH and EGF, the interaction between GH and EGF in MCF-7 cells could be transiently abrogated by GH-pre-treatment. Co-treatment with GH and EGF diminished cell viability in MCF-7 and MDA-231 cells. Furthermore, a direct influence between GH and EGF signaling resulted in less ERK phosphorylation in MCF-7 cells, whereas in MDA-231 cells less AKT phosphorylation could be observed. EGFR-down regulation due to GH is a potential reason but keeps to be elucidated
Book Synopsis Role of Epidermal Growth Factor Receptors and Their Ligands in Normal Mammary Epithelial and Breast Cancer Cells by :
Download or read book Role of Epidermal Growth Factor Receptors and Their Ligands in Normal Mammary Epithelial and Breast Cancer Cells written by and published by . This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Special Distribution of the EGF Receptor System in the Regulation of Breast Epithelia Cell Growth and Organization by :
Download or read book Special Distribution of the EGF Receptor System in the Regulation of Breast Epithelia Cell Growth and Organization written by and published by . This book was released on 1996 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 184A1 human mammary epithelial cells (HMECs) form organotypic structures when plated on Matrigel; however, after three weeks on matrigel l84Al cells do not form polarized, glandular epithelial structures, nor do they polarize if plated onto Transwell tissue culture inserts. Therefore, i84Ais can not he used to address the primary aim of my proposal: to determine if the loss of the correct spatial organization or inappropriate expression of the EGF-R system provides a growth advantage, enhances motility, or changes the differentiated state of normal cells. MCF-7 cells do express a phenotype consistent with polarized epithelia when plated on Transwells, however, MCF-7 are so loosely adherent to transwells that they are refractory to typical experimental manipulation. HB2 cells are a normal, non-transformed mammary epithelial cell line that expresses high numbers of EGF-R, are tightly adherent to transwells, and polarize on transwells as determined by immunofluorescence localization of ZO-1, the EGF-R and Beta-1 integrin. HB2 may provide an experimental system with which to address the primary of my proposal. Preliminary experiments comparing 184A1s and HB2 have revealed an interesting and novel finding--rapid internalization of EGF-R can be uncoupled from the normal negative regulatory process of down-regulation.
Book Synopsis Integrated Analysis Reveals that STAT3 is Central to the Crosstalk Between HER/ErbB Receptor Signaling Pathways in Human Mammary Epithelial Cells by :
Download or read book Integrated Analysis Reveals that STAT3 is Central to the Crosstalk Between HER/ErbB Receptor Signaling Pathways in Human Mammary Epithelial Cells written by and published by . This book was released on 2014 with total page 13 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human epidermal growth factor receptors (HER, also known as ErbB) drive cellular proliferation, pro-survival and stress responses by activating several downstream kinases, in particular ERK, p38, JNK (SAPK), the PI3K/AKT, as well as various transcriptional regulators such as STAT3. When co-expressed, first three members of HER family (HER1-3) can form homo- and hetero-dimers. Based on the considerable evidence which suggest that every receptor dimer activates intracellular signaling pathways differentially, we hypothesized that the HER dimerization pattern is a better predictor of downstream signaling than the total receptor activation levels. We validated our hypothesis using a combination of model-based analysis to quantify the HER dimerization patterns and multi-factorial experiments where HER dimerization patterns and signaling crosstalk were rationally perturbed. We have measured the activation of HER1-3 receptors and of the sentinel signaling proteins ERK, AKT, p38, JNK, STAT3 as a function of time in a panel of human mammary epithelial (HME) cells expressing different levels of HER1-3 stimulated with various ligand combinations. Our analysis using multiple ways of clustering the activation data has confirmed that the HER receptor dimer is a better predictor of the signaling through p38, ERK and AKT pathways than the total HER receptor expression and activation levels. Targeted inhibition studies to identify the causal effects allowed us to obtain a consensus regulatory interaction model, which revealed that STAT3 occupies a central role in the crosstalk between the studied pathways.
Book Synopsis The Effect of Amphiregulin and NF-kB/IL-1 Autoinductive Loops on the Proliferative, Invasive, and Migratory Properties of Human Breast Cancer Cells by : Nicole Erickson Willmarth
Download or read book The Effect of Amphiregulin and NF-kB/IL-1 Autoinductive Loops on the Proliferative, Invasive, and Migratory Properties of Human Breast Cancer Cells written by Nicole Erickson Willmarth and published by . This book was released on 2007 with total page 514 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis In Vitro Hormonal Regulation of Epidermal Growth Factor and Glucocorticoid Receptors in a Rat Mammary Tumor Clonal Line by : Ladan Basiripour
Download or read book In Vitro Hormonal Regulation of Epidermal Growth Factor and Glucocorticoid Receptors in a Rat Mammary Tumor Clonal Line written by Ladan Basiripour and published by . This book was released on 1986 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book ダブルクライシス written by and published by . This book was released on 1965 with total page 50 pages. Available in PDF, EPUB and Kindle. Book excerpt: Raised to be a thief, blind orphan Peter Nimble, age ten, steals from a mysterious stranger three pairs of magical eyes, that lead him to a hidden island where he must decide to become a hero or resume his life of crime.
Book Synopsis Regulated Transformation of Mammary Epithelial Cells by Transforming Growth Factor Beta 1 by :
Download or read book Regulated Transformation of Mammary Epithelial Cells by Transforming Growth Factor Beta 1 written by and published by . This book was released on 2002 with total page 25 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
