Ultrastructural Study on the Specific Binding of Genetically Engineered Epidermal Growth Factor to Type I Collagen Fibrils

2007 ◽  
Vol 18 (6) ◽  
pp. 2137-2143 ◽  
Author(s):  
Koichi Kato ◽  
Hideki Sato ◽  
Hiroo Iwata
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Ultrastructural Study ◽  
Type I Collagen ◽  
Specific Binding ◽  
Genetically Engineered ◽  
Collagen Fibrils ◽  
Type I ◽  
Epidermal Growth

Selective Inhibition of Type I Collagen Synthesis in Osteoblastic Cells by Epidermal Growth Factor*

Endocrinology ◽  
1984 ◽  
Vol 115 (3) ◽  
pp. 867-876 ◽  
Author(s):  
RYU-ICHIRO HATA ◽  
HISAE HORI ◽  
YUTAKA NAGAI ◽  
SHIGEYASU TANAKA ◽  
MAYURI KONDO ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Selective Inhibition ◽  
Osteoblastic Cells ◽  
Type I ◽  
Epidermal Growth

scholarly journals Regulation of Tenascin-C, a Vascular Smooth Muscle Cell Survival Factor that Interacts with the αvβ3 Integrin to Promote Epidermal Growth Factor Receptor Phosphorylation and Growth

1997 ◽  
Vol 139 (1) ◽  
pp. 279-293 ◽  
Author(s):  
Peter Lloyd Jones ◽  
Julie Crack ◽  
Marlene Rabinovitch
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Survival ◽  
Type I Collagen ◽  
Type I ◽  
Tenascin C ◽  
Epidermal Growth ◽  
Β3 Integrin ◽  
Dependent Growth

Tenascin-C (TN-C) is induced in pulmonary vascular disease, where it colocalizes with proliferating smooth muscle cells (SMCs) and epidermal growth factor (EGF). Furthermore, cultured SMCs require TN-C for EGF-dependent growth on type I collagen. In this study, we explore the regulation and function of TN-C in SMCs. We show that a matix metalloproteinase (MMP) inhibitor (GM6001) suppresses SMC TN-C expression on native collagen, whereas denatured collagen promotes TN-C expression in a β3 integrin– dependent manner, independent of MMPs. Floating type I collagen gel also suppresses SMC MMP activity and TN-C protein synthesis and induces apoptosis, in the presence of EGF. Addition of exogenous TN-C to SMCs on floating collagen, or to SMCs treated with GM6001, restores the EGF growth response and “rescues” cells from apoptosis. The mechanism by which TN-C facilitates EGF-dependent survival and growth was then investigated. We show that TN-C interactions with αvβ3 integrins modify SMC shape, and EGF- dependent growth. These features are associated with redistribution of filamentous actin to focal adhesion complexes, which colocalize with clusters of EGF-Rs, tyrosine-phosphorylated proteins, and increased activation of EGF-Rs after addition of EGF. Cross-linking SMC β3 integrins replicates the effect of TN-C on EGF-R clustering and tyrosine phosphorylation. Together, these studies represent a functional paradigm for ECM-dependent cell survival whereby MMPs upregulate TN-C by generating β3 integrin ligands in type I collagen. In turn, αvβ3 interactions with TN-C alter SMC shape and increase EGF-R clustering and EGF-dependent growth. Conversely, suppression of MMPs downregulates TN-C and induces apoptosis.

Epidermal growth factor affects the synthesis and degradation of type I collagen in cultured human dermal fibroblasts

2006 ◽  
Vol 25 (4) ◽  
pp. 202-212 ◽  
Author(s):  
Yoshihiro Mimura ◽  
Hironobu Ihn ◽  
Masatoshi Jinnin ◽  
Yoshihide Asano ◽  
Kenichi Yamane ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Type I Collagen ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Human Dermal Fibroblasts ◽  
Epidermal Growth ◽  
Synthesis And Degradation

scholarly journals Immunocytochemical study of collagen in epidermal growth factor (EGF)-treated osteoblastic cells.

1984 ◽  
Vol 32 (11) ◽  
pp. 1231-1233 ◽  
Author(s):  
Y Osaki ◽  
M Tsunoi ◽  
Y Hakeda ◽  
K Kurisu ◽  
M Kumegawa
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Type I Collagen ◽  
Osteoblastic Cells ◽  
Type Iii Collagen ◽  
Type I ◽  
Immunocytochemical Study ◽  
Type Iii ◽  
Epidermal Growth ◽  
And Control

The alteration of collagen components in clone MC3T3-E1 cells by epidermal growth factor (EGF) was investigated immunocytochemically, using antibodies to type I and type III collagens. EGF transformed those cells that had become more slender than those of control cultures. Type I and type III collagens were observed in the same cells in both EGF-treated and control cultures. Type I collagen was decreased by EGF, whereas type III collagen appeared to be increased. However, no cells with only type III collagen were observed, suggesting that EGF influences collagen metabolism in clone MC3T3-E1 cells.

Recent Advances on Epidermal Growth Factor Receptor as a Molecular Target for Breast Cancer Therapeutics

2020 ◽  
Vol 21 ◽  
Author(s):  
Swathi R. Shetty ◽  
Ragini Yeeravalli ◽  
Tanya Bera ◽  
Amitava Das
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Type I ◽  
Egfr Inhibition ◽  
Epidermal Growth

: Epidermal growth factor receptor (EGFR), a type-I transmembrane protein with intrinsic tyrosine kinase activity is activated by peptide growth factors such as EGF, epigen, amphiregulin, etc. EGFR plays a vital role in regulating cell growth, migration, and differentiation in various tissue-specific cancers. It has been reported to be overexpressed in lung, head, and neck, colon, brain, pancreatic, and breast cancer that trigger tumor progression and drug resistance. EGFR overexpression alters the signaling pathway and induces cell division, invasion, and cell survival. Our prior studies demonstrated that EGFR inhibition modulates chemosensitivity in breast cancer stem cells thereby serving as a potential drug target for breast cancer mitigation. Tyrosine kinase inhibitors (Lapatinib, Neratinib) and monoclonal antibodies (Trastuzumab) targeting EGFR have been developed and approved by the US FDA for clinical use against breast cancer. This review highlights the critical role of EGFR in breast cancer progression and enumerates the various approaches being undertaken to inhibit aggressive breast cancers by suppressing the downstream pathways. Further, the mechanisms of action of potential molecules at various stages of drug development as well as clinically approved drugs for breast cancer treatment are illustrated.

Ontogeny of epidermal growth factor receptor tyrosine kinase in rat liver

1991 ◽  
Vol 260 (2) ◽  
pp. G290-G298 ◽  
Author(s):  
B. K. De ◽  
T. L. Brown ◽  
F. J. Suchy
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Rat Liver ◽  
Plasma Membranes ◽  
Egf Receptor ◽  
Specific Binding ◽  
Liver Plasma Membranes ◽  
Epidermal Growth ◽  
Autokinase Activity

The binding of epidermal growth factor (EGF) to its receptor and the activity of the receptor intrinsic protein-tyrosine kinase were studied during the ontogeny of rat liver. The number of EGF receptors during pre- and postnatal development was first compared in crude liver plasma membranes using 1) specific binding of 125I-labeled EGF and 2) immunoblot analysis using any antireceptor polyclonal rabbit antibody. Both methods detected the expression of the EGF receptor in fetal rat liver on day 17 of gestation, but in an amount markedly less than the adult. Within 24 h, there was a more than twofold increase in EGF binding to plasma membranes as well as a marked increase in receptor immunoreactivity. However, after birth, there was a precipitous drop in receptor number to less than 20% of the adult level by the end of the first postnatal day (P less than 0.001). Next, the presence of EGF-stimulated tyrosine kinase activity (autophosphorylation) was determined during the same stages of development. Electrophoresis of membranes phosphorylated in the presence or absence of EGF followed by autoradiography demonstrated autokinase activity stimulated by EGF in day 18 and 19 fetal liver plasma membranes, but not in membranes on day 17 of gestation. Similar to the pattern observed with EGF binding, there was a decrease in autokinase activity in early neonatal plasma membranes followed by an increase to near adult levels by 7 days postnatally. Quantitation of the amount of 32P radioactivity associated with the EGF receptor bands in each age group, correlated with the degree of autophosphorylation assessed by autoradiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetic analysis of the downregulation of epidermal growth factor receptors in rats in vivo

1990 ◽  
Vol 258 (4) ◽  
pp. C593-C598 ◽  
Author(s):  
S. Yanai ◽  
Y. Sugiyama ◽  
T. Iga ◽  
T. Fuwa ◽  
M. Hanano
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Surface ◽  
Kinetic Analysis ◽  
Intravenous Administration ◽  
Recovery Rate ◽  
Specific Binding ◽  
Control Level ◽  
Epidermal Growth

We previously clarified the specific binding sites for epidermal growth factor (EGF) in several organs in rats based on in vivo kinetic analysis (D. C. Kim, Y. Sugiyama, H. Sato, T. Fuwa, T. Iga, and M. Hanano. J. Pharm. Sci. 77: 200-207, 1988). In the present study, we have determined the extent of the receptor downregulation and the recovery rate of the available receptors for EGF in several organs in vivo. At the specified times (30 min-24 h) after intravenous administration of excess unlabeled EGF (300 micrograms/kg), the early-phase (less than 3 min) uptake clearances (k1) of the tracer amount of 125I-EGF, which are proportional to the cell-surface available receptor densities, were determined in the liver, kidney, duodenum, jejunum, ileum, stomach, and spleen. As the result, the k1 value in each organ at 30 min after intravenous administration of unlabeled EGF was lowered close to the receptor-independent clearance value, indicating that the cell-surface receptors were almost completely downregulated, and thereafter, the k1 value showed gradual recovery to the control level. Furthermore, the recovery half-lives showed interorgan differences, namely the half-life (20 min) in the liver was much shorter than those (2-4.5 h) in other organs. These results were considered to reflect the processes of the recycling of internalized EGF receptors to the cell-surface or recruitment of new receptors. It was concluded that the recovery rate of the downregulated receptors in the liver, which is most responsible for the plasma clearance of EGF, is much faster than those in other organs.

Segmental distribution of epidermal growth factor binding sites in rabbit nephron

1990 ◽  
Vol 259 (4) ◽  
pp. F553-F558 ◽  
Author(s):  
M. D. Breyer ◽  
R. Redha ◽  
J. A. Breyer
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transforming Growth Factor ◽  
Specific Binding ◽  
Rabbit Kidney ◽  
Egf Receptors ◽  
Collecting Ducts ◽  
Epidermal Growth ◽  
Sites Of Action ◽  
Convoluted Tubules

The kidney possesses epidermal growth factor (EGF) receptors and is a major site of synthesis for the EGF precursor, prepro-EGF. To examine the segmental localization of EGF receptors in the rabbit kidney, we characterized 125I-labeled EGF binding to micro-dissected rabbit nephron segments. Specific binding constituted 70-80% of total binding and was saturable with an apparent Kd of 8 nM. Kinetic studies (0 degrees C) revealed an association t1/2 of 20.7 min and a dissociation t1/2 of 27 min. Competition studies revealed that 125I-EGF binding was inhibited by unlabeled EGF or its homologue transforming growth factor-alpha, but not by parathyroid hormone or insulin. Mapping studies showed specific 125I-EGF binding (attomoles per centimeter) was highest in proximal straight tubules, followed by proximal convoluted tubules, cortical collecting ducts, inner medullary collecting ducts, outer medullary collecting ducts, and distal convoluted tubules. Specific binding to glomeruli was also observed. Interestingly, no specific binding of 125I-EGF to thick ascending limbs, a site of EGF precursor synthesis, was observed. These studies suggest potential sites of action for EGF in the rabbit kidney.

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