| 26694612 | COCs expanded in vitro with FSH or EGF underwent the same changes, whereas those expanded with 8-bromo-adenosine-3',5'-cyclic monophosphate (8-Br-cAMP) maintained integrity for a longer time |
| 25367123 | EGF promotes mammalian cell growth by suppressing cellular senescence |
| 24491556 | We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs) |
| 24491556 | FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2 |
| 24055032 | Clinical significance of proliferation, apoptosis and senescence of nasopharyngeal cells by the simultaneously blocking EGF, IGF-1 receptors and Bcl-xl genes |
| 24055032 | BACKGROUND: In previous work, we constructed short hairpin RNA (shRNA) expression plasmids that targeted human EGF and IGF-1 receptors messenger RNA, respectively, and demonstrated that these vectors could induce apoptosis of human nasopharyngeal cell lines (CNE2) and inhibit ligand-induced pAkt and pErk activation |
| 24047696 | Moreover, aberrant EGF receptor (EGFR) activation triggered IL-6 synthesis |
| 23746120 | Furthermore, our results showed that Mig-6 induction of senescence is related to its inhibition of EGF receptor (EGFR)/Erb B signalling |
| 21852385 | EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks |
| 20833136 | Depletion of Nup107 by specific siRNA in young human diploid fibroblasts prevented the effective nuclear translocation of phosphorylated extracellular signal-regulated kinase (ERK) following epidermal growth factor (EGF) stimulation, and decreased the expression of c-Fos in consequence |
| 20300111 | Jun(d/d) mouse embryonic fibroblasts (MEFs) exhibit early senescence, which can be rescued by EGF and HB-EGF stimulation, probably through activation of Akt signaling |
| 17266044 | This immortalization required short-term EGF treatment near the time of crisis |
| 16600555 | By use of conditioned medium, we found a growth promoting impact of fibroblasts compared with control medium from epithelial cells associated with activation of ERK1/2, Akt, p70S6K, and EGF receptor |
| 16170353 | However, tyrosine phosphorylation of the receptors for EGF and IGF-I and Akt/PKB activation were unaltered by Sirtinol treatment |
| 15946240 | In this study, we have investigated the age-related alteration of responses to epidermal growth factor (EGF) in cultured human keratinocytes that were senesced in vitro by repeated passage |
| 15946240 | Western blot analysis demonstrated that EGF induced dramatic increase in the phosphorylation of EGF receptor (EGFR) and extracellular signal-regulated kinases (ERK) in young cells, while this phosphorylation was much less profound in senescent cells |
| 15658102 | Nevertheless, unlike the rat C6 glioma cell line, these immortalized cell lines demonstrate EGF dependence and low clonogenicity in soft agar and did not form tumors after intracranial transplantation |
| 14743960 | Pretreatment of ME180S cells with epidermal growth factor (EGF) inhibits IFN-dependent induction of p53 and p21 by protein kinase C dependent pathways |
| 14499637 | Aging-related attenuation of EGF receptor signaling is mediated in part by increased protein tyrosine phosphatase activity |
| 12593448 | The role of epidermal growth factors (EGF) and transforming growth factors (TGF) alpha and beta as autocrine factors in inducing senescence of cultured HMEC cells were also investigated |
| 12593448 | Deletion of EGF from growth media initially caused decreased proliferation to target HMEC cells, followed by improvement in their proliferation |
| 12593448 | The morphologic and phenotypic characteristics of target HMEC cells exposed to TGF-alpha were also found similar to those HMEC cells grown during primary culture, suggesting autocrine production of EGF and TGF-alpha by cultured HMEC cells during primary culture |
| 12593448 | Exposure of senescent cells to media supplemented with EGF and TGF-alpha could not induce their proliferation |
| 12373308 | Cells of SHEE14, SHEE20 and SHEE30 were examined according to cell morphology, cell cycle, apoptosis, contact-inhibition growth, anchorage- dependency, dose-dependency to epithelial growth factors (EGF), telomerase activity and tumorigenicity |
| 12373308 | The different response to dose-dependency to EGF was not statistically different in SHEE14 and SHEE30 |
| 12373308 | Compared with SHEE14 and SHEE20, SHEE30 cells were of immortalized status with immortal phenotype, which consisted of telomerase activity, increase of cell proliferation, weakened contact-inhibition and anchorage-dependent growth, dose dependency to EGF and lack of tumor formation |
| 12044940 | The overexpression of caveolins caused senescent-like changes in epidermal growth factor (EGF) response of the young cells, while down regulation of caveolins by use of antisense-oligonucleotides restored the EGF response in old cells, suggesting that caveolin system would be one of the major mechanisms responsible for decreased responses to growth factors in the senescent cells |
| 11976184 | Senescent cells did not phosphorylate Erk-1/2 after EGF stimulation, whereas young cells did |
| 11976184 | When we overexpressed caveolin-1 in young HDF, the activation of Erk-1/2 on EGF stimulation was significantly suppressed |
| 11976184 | These results suggest that the hyporesponsiveness of senescent fibroblasts to EGF stimulation might be due to the overexpression of caveolin |
| 11795531 | Attenuation of EGF signaling in senescent cells by caveolin |
| 11795531 | One of the characteristics of senescent cells is unresponsiveness to external stimuli like EGF |
| 11795531 | Although they have a normal level of receptors and downstream signaling molecules, EGF cannot induce the activation of Erk kinases and DNA synthesis in senescent cells as much as in young cells |
| 11795531 | Caveolin proteins directly interact with signaling molecules including EGF receptor and suppress the activation of EGFR upon EGF stimulation |
| 11795531 | We found that Erk activation after EGF stimulation in senescent human diploid fibroblasts was down-regulated |
| 11795531 | From these results, we suggest that the up-regulated expression of caveolin might explain the unresponsiveness of senescent fibroblasts to EGF stimulation |
| 11795508 | Senescent HDF cells as well as the H-ras mutant expressers accumulated p-Erk1/2 in the cytoplasm with increased MEK activity and failed to translocate it to nuclei on EGF stimulation |
| 11080532 | Senescent HDF cells as well as the H-ras mutant expressers accumulated p-Erk1/2 in the cytoplasm with increased MEK activity and failed to translocate it to nuclei on EGF stimulation |
| 10781609 | Senescent human diploid fibroblasts do not respond to growth factors like epidermal growth factor (EGF), although they have a normal level of receptors and downstream signaling molecules |
| 10781609 | To examine the mechanism of signaling attenuation, we investigated Erk activation after EGF stimulation in senescent cells |
| 10781609 | Senescent cells did not phosphorylate Erk-1/2 after EGF stimulation, whereas young cells did |
| 10781609 | In those senescent cells, we found an increased level of caveolin proteins and strong interactions between caveolin-1 and EGF receptor |
| 10781609 | However, in the case of p53-induced senescence, caveolin-1 was not induced, and EGF stimulation phosphorylated Erk-1/2 as much as young control cells |
| 10781609 | Finally, we overexpressed caveolin-1 in young human diploid fibroblasts in which the activation of Erk-1/2 upon EGF stimulation was significantly suppressed |
| 10781609 | These results suggest that the unresponsiveness of senescent fibroblasts to EGF stimulation may be due to the overexpression of caveolins, which seems to be independent of growth arrest and other aging phenotypes |
| 10764734 | Aging fibroblasts present reduced epidermal growth factor (EGF) responsiveness due to preferential loss of EGF receptors |
| 10764734 | Thus, as cells approach senescence, programmed in vivo or in vitro, EGF responsiveness is preferentially lost |
| 10764734 | To define the rate-limiting signaling event, we found that the activity of two different EGF receptor (EGFR)-signaling pathways to cell migration (phospholipase-C gamma) and/or mitogenesis (extracellular signal/regulated-mitogen-activated kinases) were decreased in near senescent cells despite unchanged levels of effector molecules |
| 10764734 | Since these data suggested that the decrement in EGF was rate-limiting, higher levels of EGFR were established in near senescent cells by electroporation of EGFR cDNA |
| 10764734 | Thus, the defect in EGF responsiveness of aged dermal fibroblasts is secondary to reduced EGFR message transcription |
| 10751218 | We found that the cytosolic Ca(2+) release triggered by either ionomycin or by several IP(3)-generating mitogens, namely bradykinin, thrombin, platelet-derived growth factor (PDGF), and epidermal growth factor (EGF), was attenuated markedly in senescent HDFs |
| 10751218 | However, the response latency seen with both PDGF and EGF was greater for senescent cells |
| 10751218 | In parallel, IP(3) formation in response to bradykinin or EGF was also attenuated in senescent HDFs |
| 10674820 | Withdrawal of either EGF or amphiregulin from medium resulted in down-regulation of telomerase activity |
| 9642304 | OBJECTIVE: To observe the changes of proto-oncogene c-fos/c-myc expression and its relation to specific transcription factors in human senescent fibroblast after epidermal growth factor (EGF) addition |
| 9642304 | RESULTS: (1) The expression of c-fos/c-myc was less susceptible to induction by EGF as the cells aged |
| 9642304 | CONCLUSIONS: Inability of c-fos/c-myc gene induction by EGF in senescent cells might be correlated with some DNA-binding proteins |
| 8892981 | This repression depends on the presence of growth factors, specifically EGF, and requires protein synthesis |
| 7564558 | After both cells were treated by FGF or epidermal growth factor (EGF), Rb expression increased 210-275% in young cells and 50-60% in old ones |
| 8082719 | The molecular basis of this reduction and the effects of the calcium ionophore A23187 and epidermal growth factor (EGF) on young and old HUVEC have been investigated |
| 8082719 | While both young and senescent cells responded immediately to increases in intracellular calcium concentrations, only young cells produced a dose-dependent decrease in cell coupling in response to the addition of exogenous EGF |
| 8082719 | The inability of senescent cells to down-regulate gap junctions in response to EGF reflects a defect in the regulatory mechanism of gap junction activity in senescent cells |
| 8077280 | Numerous studies suggest that epidermal growth factor (EGF) signaling is impaired in nonproliferating senescent human diploid fibroblasts downstream of receptor binding |
| 8077280 | One possible explanation for these results is that senescent cells possess unique enzymatic activities capable of regulating functional levels of the EGF receptor |
| 8077280 | To test that hypothesis, nonionic detergent lysates of young and senescent cells were compared for proteolytic activity directed towards the EGF receptor, and a protease that cleaves the 170 kDa EGF receptor was identified in lysates from senescent but not young cells |
| 8077280 | The degradation product immunoprecipitated by a monoclonal antibody specific for an EGF receptor exocytosolic epitope had an approximate molecular weight of 100,000 |
| 8077280 | Interestingly, this protease was not active during ligand-induced intracellular processing of the EGF receptor, suggesting that it does not normally function in endocytic or lysosomal compartments |
| 8077280 | Since EGF receptor cleavage is not observed unless senescent cells are solubilized with nonionic detergents, it seems likely that the protease is confined to specialized regions of the plasma membrane |
| 8077280 | Whether or not the EGF receptor is a physiologic target for this protease is unclear |
| 8106562 | We have previously found that stimulation of normal neonatal fibroblasts with PDGF or EGF leads to a transient induction of PDGF A-chain mRNA and the synthesis of PDGF-AA proteins |
| 8028398 | We examined the proliferative response of 2BS cells of different population doubling levels to epidermal growth factor (EGF) |
| 8028398 | As the cells aged, there was a significant decrease both in the baseline level of DNA synthesis and in the stimulation of DNA synthesis by EGF addition |
| 8028398 | The effective concentration of EGF and the latent period prior to DNA synthesis did not change |
| 8028398 | EGF receptor mRNA expression also remained unchanged as the cells aged, in the absence or presence of EGF, suggesting that the defect in old cells lies downstream in the EGF signaling pathway |
| 8028398 | As the cells reached 100% of their life span, however, there was a 70% decrease in EGF receptor mRNA |
| 8028398 | Expression of the EGF receptor homologue HER-2 was also examined |
| 8028398 | Moreover, HER-2 expression was stimulated by EGF addition in young cells but not in old cells |
| 8018955 | These cells overexpressed p53 protein and had an amplified epidermal growth factor (EGF) receptor gene that resulted in high level expression of tyrosine phosphorylated EGF receptor protein |
| 8018955 | Despite the presence of high levels of tyrosine phosphorylated EGF receptor in these cells, they proliferated in serum-free, EGF-free medium and did not secrete detectable levels of EGF-like mitogenic growth factor |
| 8018955 | In addition, these cells were potently growth inhibited by all concentrations of exogenous EGF tested and by the neutralizing EGF receptor antibody Mab 425 |
| 8018955 | These results suggest that the high level of tyrosine phosphorylated EGF receptor present in these cells is the direct result of receptor overexpression and not the result of the presence of a stimulatory ligand |
| 8223996 | Epidermal growth factor (EGF) is a well-characterized mitogen whose effectiveness decreases with age both in vivo and in vitro |
| 8223996 | In contrast, we now report striking differences in EGF receptor (EGFR) number, affinity, and rate of EGF/EGFR internalization in early-passage dermal fibroblasts derived from newborn versus young adult versus old adult donors |
| 8223996 | These data demonstrate critical differences between the two models of cellular aging, provide an explanation for the age-associated loss of EGF responsiveness, and may explain in part the tendency toward impaired wound healing in the elderly |
| 8376318 | These cells respond to the combination of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and dexamethasone by DNA synthesis at a rate and extent equivalent to serum-stimulated cells |
| 8376318 | TNF stimulated an increase in the number of EGF specific binding sites two- to threefold in 24 h in both young and senescent cells |
| 8376318 | IFN-beta has little or no effect on EGF binding either alone or in combination with TNF |
| 1537881 | In this study, we compared the responsiveness to EGF of late passaged (senescent) human omental microvascular endothelial (HOME) cells with that of early passaged (young) HOME cells |
| 1537881 | Scatchard analysis demonstrated that the number for both high and low affinity receptors for EGF in HOME cells was decreased dramatically during serial cultivation |
| 1537881 | The expression of EGF receptor mRNA was also decreased in the senescent HOME cells |
| 1537881 | Treatment of HOME cells with EGF significantly increased cellular mRNA levels of tissue-type plasminogen activator, and two protooncogenes, c-fos and c-myc, in young HOME cells, but not in senescent HOME cells |
| 1537881 | Thus HOME cells aged in vitro show a decreased responsiveness to EGF, resulting in decreased migration of human endothelial cells |
| 1537881 | The serial cultivation of human endothelial cells in vitro may downregulate EGF receptor and decrease responsiveness to exogenous EGF, a potent angiogenic factor |
| 1389230 | Epidermal growth factor (EGF) stimulates the mitosis and differentiation of a variety of cellular types |
| 1389230 | The cell types emerging from glomeruli cultured with and without EGF were compared and identified by morphological, immunofluorescence and electron microscopy criteria |
| 1389230 | Two cell types: visceral epithelial cells or podocytes (type I) and mesangial cells (type II) emerged from glomeruli cultivated without EGF |
| 1389230 | A third cell type, called type III cells, appeared only in the presence of EGF |
| 1389230 | We suggest that type III epithelial-like cells are precursor cells of podocytes, that EGF triggers their emergence from glomeruli and their subsequent proliferation and differentiation in vitro |
| 1389230 | EGF also prolongs their lifetime in culture |
| 1716619 | The authors tried to determine whether human corneal endothelial cells in primary culture synthesize messenger RNA (mRNA) coding for epidermal growth factor (EGF), EGF receptor, basic fibroblast growth factor (FGFb), transforming growth factor beta-1 (TGFb1), and interleukin-1 alpha (IL-1 alpha) |
| 1716619 | The polymerase chain reaction (PCR) was used to amplify the growth factors (EGF, FGFb, TGFb1, and IL-1 alpha), EGF receptor, and beta actin sequences from each of the cDNA samples |
| 1716619 | The EGF receptor, FGFb, and beta actin mRNAs were present in all eight cDNA samples |
| 1716619 | The EGF mRNAs were detected by PCR alone in four of the samples from proliferative cultures, TGFb1 mRNAs in three, and IL-1 alpha mRNAs in three |
| 1847336 | EGFWe have examined the ability of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) to stimulate cultures of young and senescent WI-38 cells to carry out tyrosine-specific phosphorylation of their respective membrane receptors |
| 1847336 | Furthermore, we found no differences in the EGF- or PDGF-stimulated phosphorylation of their respective receptors in intact cells |
| 1847336 | These data support the previous findings that although the EGF receptor autokinase activity becomes highly labile during extraction and immunoprecipitation of senescent cells, in situ loss of receptor tyrosine kinase activity is apparently not responsible for the age-associated loss of mitogenic responsiveness |
| 2365743 | Human diploid fibroblasts (HDF) were used to study aging-related changes in the proliferative response to platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and insulin-like growth factor I (IGF-I, somatomedin-C) in serum-free, chemically defined culture medium |
| 2365743 | PDGF and EGF exert their primary effect upon regulation of the proportion of cycling cells in the culture |
| 2365743 | The doses of PDGF and EGF that produced a half-maximal cycling fraction, analogous to Km, showed no large or consistent difference between young- and old-passage cells |
| 2365743 | In summary, among cells capable of cycling in aging cultures, there were few changes in the regulation of the growth fraction by PDGF and EGF, but there was a greatly increased dependence on IGF-I for regulation of the rate of entry into S phase |
| 2632278 | We present examples of four types of alterations which contribute to the senescence phenotype of WI-38 cells: a) in senescent cells there is an increased lability of the tyrosine autophosphorylation capacity of detergent isolated EGF receptor; b) following serum stimulation, the calmodulin protein level fails to increase in senescent cells, although the calmodulin mRNA level increases as expected; c) following heat shock at 43 degrees C, senescent cells produce both less RNA and less protein for the HSP70 and HSP90 genes; d) we find that membranes isolated in basic buffer from senescent or young cells increase the EGF proliferative response of senescing cells, in contrast to the finding by others that membranes isolated in neutral buffer inhibit cell proliferation (Pereira-Smith et al |
| 3320064 | EGF-dependent phosphorylation of the EGF receptor in plasma membranes isolated from young and senescent WI-38 cells |
| 3320064 | Tyrosine-specific phosphorylation of the receptor for epidermal growth factor (EGF) in plasma membranes isolated from WI-38 cells is EGF-dependent and occurs to an equivalent extent and on identical tryptic peptides in preparations from cells of various in vitro ages |
| 3320064 | This finding provides a marker for senescence and suggests subtle changes in protein structure, conformation, or regulation of the EGF receptor in senescent cells |
| 2959670 | 8 microM) in a serum-free medium containing epidermal growth factor (EGF) (16 nM) and dexamethasone (DEX) (140 nM) and stimulate DNA synthesis in young cultures of WI-38 cells, similar to the stimulation of serum-supplemented medium |
| 2959670 | The effect of IGF-I, EGF, and DEX is synergistic in stimulating multiple rounds of low density cell division |
| 3494524 | TGF-beta inhibition of endothelial cell proliferation: alteration of EGF binding and EGF-induced growth-regulatory (competence) gene expression |
| 3494524 | These changes are accompanied by a decrease in the number of high-affinity receptors for epidermal growth factor (EGF), with almost no change in total receptor number |
| 3494524 | Additionally, the EGF-induced expression of specific competence genes (c-myc, JE, KC) is decreased, whereas the induction of c-fos gene expression by EGF is unaltered by TGF-beta treatment |
| 3011471 | 1 nM epidermal growth factor (EGF) resulted in a synergistic increase in proliferation and final cell density |
| 3011471 | The action of DEX plus EGF was stimulatory but not synergistic in young confluent cultures |
| 3011471 | DEX plus EGF had no synergistic effect on senescent cells either during log phase or at confluence |
| 3012222 | Cellular responsiveness to epidermal growth factor (EGF) and the structure of the receptor for epidermal growth factor (EGF-R) were compared in young and senescent human fibroblast (HF) cells |
| 3012222 | Autophosphorylation of EGF-R in response to EGF was identical in young and senescent cells |
| 3012222 | The responsiveness of aging HF cells to EGF for the induction of ornithine decarboxylase activity and for the production of secretory proteins was measured |
| 3012222 | Young and senescent HF cells showed about a three-fold induction of collagenase activity upon addition of EGF |
| 3012222 | Ornithine decarboxylase activity was also stimulated by EGF to a comparable level in young and senescent cells |
| 3012222 | Our results indicate that the responsiveness of HF cells to EGF for these two biochemical parameters does not decline with the loss of proliferative activity |
| 2998327 | EGF has been of particular interest since it is so well characterized |
| 6300148 | Using a serum-free medium supplemented with hormones and growth factors, which included epidermal growth factor (EGF), we investigated the binding and processing-degradation of [125I]EGF in WI-38 cells of various in vitro ages |
| 6300148 | Thus, EGF binding does not decrease in senescence |
