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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors evaluated the effects of stimulation (by serum, wounding, and three peptide growth factors: fibroblast growth factor [FGF], insulin, and transforming growth factor-beta [TGF-beta 1]) on the expression of the protein product of the immediate early gene, c-fos in bovine corneal endothelial (BCE) cells. These results were compared with those of cells which were made quiescent by serum starvation. They also examined the effect of these same growth factors or wounding on DNA synthesis. Quiescent cells expressed low levels of c-fos protein. Serum was the most potent stimulator, whereas FGF and insulin were modest stimulators. TGF-beta 1 did not significantly stimulate c-fos protein production. The results from DNA synthesis were different. Serum and FGF were still the most potent stimulators; insulin and TGF-beta 1 were weak stimulators. These data suggest that growth factors induce c-fos protein in BCE cells and that this may in part regulate the downstream event, cellular proliferation. Further investigation into the regulation of this and other protooncogene products may provide insight into the mechanisms which modulate corneal endothelial cell growth in humans.
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PMID:Fos expression and growth regulation in bovine corneal endothelial cells. 142 6

Structural heterogeneity has been demonstrated for growth hormone (GH) receptors from a number of species, and both high and low affinity art receptors have been characterised by ligand binding studies. In the present study, we have transfected Chinese hamster ovary (CHO-K1) cells with a cDNA clone encoding a full-length transmembrane ovine (o) GH receptor, under the regulatory control of the human metallothionein IIA promoter. A stably transfected cell line was established (GHR9.5) which expresses on the cell surface a single class of receptor which binds 220,000 [125I]oGH molecules at high affinity (Kd = 0.30 nM) which is comparable to the affinity established for endogenous oGH receptors in postnatal sheep liver microsomes (Kd = 0.27 nM, Freemark et al. (1987) Endocrinology 120, 1865-1872). The expressed receptor also binds ovine placental lactogen (oPL, 205,000 binding sites per cell) with high affinity (Kd = 0.76 nM). The presence of two species of oGH receptor was detected in GHR9.5 cells using affinity cross-linking analysis (M(r) 148,000 and M(r) 73,000) and given that the oGH receptor cDNA codes for a non-glycosylated receptor of M(r) 69,914, it is likely that these cross-linked species correspond to homodimeric and monomeric forms of the oGH receptor, each binding to a single molecule of GH. Parallel cross-linking studies with sheep liver microsomes also demonstrated two oGH receptor species (M(r) 133,000 and M(r) 58,000), the difference in relative molecular weights between the transfected and endogenous receptors presumably resulting from tissue-specific post-translational modifications. In the presence of oGH, the GHR9.5 cells respond by increasing total cellular protein synthesis by 27% relative to non-GH-exposed GHR9.5 cells, indicating the functionality of the expressed receptor. We also demonstrate unequivocally that oPL, through a specific interaction with the transfected oGH receptor, is able to mediate a similar cellular response (38% protein synthesis induction). Responsiveness to oGH and oPL in the GHR9.5 cells is dependent on serum starvation prior to oGH exposure and occurs only with prolonged exposure (greater than 2 h) to oGH. This cellular stimulation occurs independently of c-fos transcription which has previously been shown to be one of the earliest events associated with GH action in tissues expressing endogenous GH receptors (Doglio et al. (1989) Proc. Natl. Acad. Sci. USA 86, 1148-1152; Slootweg et al. (1990) J. Mol. Endocrinol. 4, 265-274).
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PMID:Functional expression of an ovine growth hormone receptor in transfected Chinese hamster ovary cells. 151 79

Induction of c-fos mRNA levels associated with the stimulation of growth by fetal bovine serum following quiescence was examined in three cell types following brief (24 h) serum starvation. Starved NIH-3T3 and HeLa S3 cells experienced c-fos mRNA induction 20-30 min after addition of serum. In contrast, Swiss-3T3 cells expressed c-fos constitutively following serum starvation. The pattern of oncogene expression coincided with the level of quiescence of each cell line prior to induction. Serum inductions of c-fos expression was dependent upon the response of each cell line to serum starvation, c-fos expression was also examined in HeLa S3 cells that had been separated into sequential cell cycle phases by centrifugal elutriation, c-fos expression peaked during the earliest part of the synchronous G1 phase. The amount of c-fos mRNA measured was approximately twice that found during other cell cycle phases. This suggests that, in addition to its role during the transition from quiescence, the c-fos gene product may play a regulatory role during the earliest part of G1 phase of the continuous cell cycle.
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PMID:Variations in c-fos mRNA expression during serum induction and the synchronous cell cycle. 211 93

Genes of higher eucaryotic cells are considered to show only a limited response to nutritional stress. Here we show, however, that omission of a single essential amino acid from the medium caused a marked rise in the mRNA levels of c-myc, c-jun, junB and c-fos oncogenes and ornithine decarboxylase (ODC) in CHO cells. There was no general accumulation of mRNAs in amino acid-starved cells, since the gamma-actin, beta-tubulin, protein kinase C, RNA polymerase II, and glyceraldehyde-3-phosphate dehydrogenase mRNAs and the total poly(A)+ mRNA were not increased. The levels of c-myc, ODC, and c-jun mRNAs were elevated more by amino acid starvation than by inhibition of protein synthesis with cycloheximide, which is known to increase the levels of these mRNAs. Importantly, however, cycloheximide present during amino acid starvation reduced the rise in the levels of the mRNAs down to the level obtained with cycloheximide alone. This implies that protein synthesis is required for the accumulation of c-myc, ODC, and c-jun mRNAs in amino acid-deprived cells. The junB and c-fos mRNAs, instead, were increased to the same extent or less by amino acid starvation than by cycloheximide treatment. The accumulation of the c-myc mRNA in amino acid-starved cells was due to both stabilization of the mRNA and increase of its transcription. The rise in the c-jun mRNA level seemed to be caused merely by stabilization of the mRNA. Further, despite the inhibition of general protein synthesis, amino acid starvation led to an increase in the synthesis of c-myc polypeptide. The results suggest that mammalian cells have a specific mechanism for registering shortages of amino acids in order to make adjustments compatible with cellular growth.
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PMID:Deprivation of a single amino acid induces protein synthesis-dependent increases in c-jun, c-myc, and ornithine decarboxylase mRNAs in Chinese hamster ovary cells. 212 33

Two classes of early genes in Dictyostelium are differentially regulated by extracellular pulses of cAMP interacting with its cell-surface receptor, conditions that also regulate chemotaxis and aggregation. The pulse-repressed genes, such as K5, are induced shortly after the onset of starvation and are repressed a few hr later during aggregation by cAMP pulses. The pulse-induced genes (including D2, M3, and those encoding contact sites A, the G alpha protein subunit G alpha 2, and the cell-surface cAMP receptor) are maximally induced just prior to aggregation by pulses of cAMP and are subsequently repressed by sustained moderate levels of cAMP--conditions that exist sequentially in development. In this manuscript, we further analyze the requirement for cAMP pulses and characterize a requirement for protein synthesis for the expression of these two classes of genes. Our results indicate that the control of expression of both the pulse-induced and pulse-repressed genes requires other developmentally regulated factors in addition to starvation and cAMP pulses. We also identified another early gene, F9, whose expression is stimulated upon starvation, is not responsive to cAMP, and is hyperstimulated by cycloheximide, in a manner similar to the cycloheximide stimulation of c-fos and other serum-induced genes in mammalian cells. Examination of the kinetics of expression of the pulse-induced genes in a mutant blocked in the cAMP relay pathway indicates that their expression is controlled by a two-phase process. The first phase requires starvation and CMF, an extracellular conditioned medium factor, and results in a low level of expression. The second phase requires establishment of the cAMP signal-relay system and induces the genes to a high level. Both phases require prior and concomitant protein synthesis. Some of the members of the pulse-induced class encode elements of the cAMP signal-relay system that controls aggregation, indicating a feedback autoregulation. The two-phase process might allow the "finetuning" of the level of expression of genes involved in aggregation.
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PMID:Two-phase regulatory pathway controls cAMP receptor-mediated expression of early genes in Dictyostelium. 253 21

PC12 cells were manipulated in such a way as to permit the study of differentiation-specific responses independently from proliferative responses. Cells were starved for serum then exposed to nerve growth factor (NGF) or serum. Following addition of serum, cells incorporated thymidine in a synchronous manner. Subsequent to the wave of DNA synthesis, the cell number increased approximately two-fold. Addition of NGF to serum-starved cultures had no measurable effect on either parameter. Neurite outgrowth was more rapid and extensive and appearance of Na+ channels, measured as saxitoxin binding sites, more rapid than when NGF was added to exponentially-growing cells. Epidermal growth factor receptors were heterologously down-regulated by NGF with similar kinetics under both conditions. Induction of the proto-oncogene c-fos by NGF was also greater in the serum-starved cells than in exponentially-growing cultures. These results indicated that serum starvation resulted in synchronisation of the cultures and that NGF action may be cell cycle-specific. Analysis of the cellular response to NGF at different times during the cell cycle showed that c-fos was induced in the G1 phase but not in S or G2. Fluorescence-activated cell sorter analysis demonstrated that addition of NGF to exponentially-growing cells, resulted in their accumulation in a G1-like state. With regard to the study of the mechanism of NGF action, these results illustrate that measurements of NGF effects on specific components in the signal transduction pathway may be confounded by the use of exponentially-growing cultures.
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PMID:Cell cycle-specific action of nerve growth factor in PC12 cells: differentiation without proliferation. 255 60

Using Northern blot analysis the expression of several proto-oncogenes was studied in established lines of mast cell precursors. Upon removal of interleukin-3 (IL-3) from the culture medium, factor-dependent cells stop dividing. During the first 7 h, however, normal amounts of total cellular mRNAs are maintained, and this is reflected in unchanged levels of several transcripts, such as actin, c-Ha-ras and c-fes. In contrast, within 1.5 h of IL-3 removal, the levels of c-myc and c-fos mRNAs decrease drastically and addition of IL-3 at that stage quickly induces back the levels found in actively growing cultures. In factor-independent cells, which proliferate actively even in the absence of IL-3, high levels of c-myc and c-fos transcripts are maintained in the absence of growth factor. In cells arrested by serum starvation, addition of 10% serum induces massive amounts of c-fos transcripts, but not of c-myc, and cell proliferation is not restored. The data suggest that the c-myc and c-fos proto-oncogenes play an important role in mediating the multiple effects of IL-3 on hemopoietic progenitor cells.
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PMID:Interleukin-3-dependent expression of the c-myc and c-fos proto-oncogenes in hemopoietic cell lines. 308 85

The mRNA expression of c-myc and N-myc in the human neuroblastoma cell line SH-SY5Y was found not to change appreciably during the cell cycle and was also unaffected by proliferative inhibition induced by serum starvation or polyamine depletion. However, an early (0.5-8.0 h post-induction) transient reduction of c- and N-myc transcripts were observed in these cells upon induction to differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Treatment of these neuroblastoma cells with TPA for longer periods (1-8 days), which induces morphological and functional differentiation and growth arrest, was followed by decreased expression of both myc genes. However, the rate of disappearance differed considerably. The N-myc mRNA level was slightly decreased after 4 days and was still detectable 8 days after induction, whereas the c-myc transcript was down-regulated much faster. In contrast, when the cells were exposed to retinoic acid, which results in a maturation along an alternative pathway, the inhibition of N-myc and c-myc expression was similar. The c-fos mRNA expression increased in TPA-treated SH-SY5Y cells and remained high during extended exposure to the drug. The highest c-fos transcript level in induced cells coincided in time with the transient reduction of N-myc and c-myc. Thus, the TPA-induced neuronal differentiation of SH-SY5Y cells was compatible with high c-fos and a substantial N-myc mRNA expression.
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PMID:Different regulation of N- and c-myc expression during phorbol ester-induced maturation of human SH-SY5Y neuroblastoma cells. 332 85

The tax gene of human T lymphotropic virus type I has been implicated in the genesis of adult T cell leukemia (ATL). It has been reported that expression of tax induces neoplastic transformation in the rat fibroblast cell line Rat-1, and that co-expression with the ras gene can transform rat embryo fibroblasts. Possible activation of cellular oncogenes including c-myc and c-fos by tax has been implicated in these tax functions. In this study, comparative analysis of biological properties of tax and cellular nuclear oncogenes c-myc and c-fos was performed in Rat-1 cells. While all three oncogenes could transform Rat-1 cells, significant differences in the sensitivity to induction of apoptosis were observed between cells transformed with each oncogene. Induction of apoptosis by serum starvation was observed in tax-transfected Rat-1 cells but to a lesser extent than that in those transfected with c-myc or c-fos. In contrast, exposure to a DNA-damaging agent, etoposide, resulted in enhanced apoptotic death only in c-myc-transfected Rat-1 cells. Our findings indicate that the pathways for apoptosis induction may not be identical among these three oncogenes, and that the relatively low apoptosis-inducing activity and sufficient transforming capacity of tax might be associated with transformation of T cells and the low susceptibility of the transformed T cells (ATL cells) to chemotherapeutic agents.
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PMID:Differences in sensitivity to induction of apoptosis among rat fibroblast cells transformed by HTLV-I tax gene or cellular nuclear oncogenes. 762 22

The c-Myc protein is involved in cellular transformation and mitogenesis, but also works as a potent inducer of differentiation and programmed cell death. Max as an obligate heterodimeric partner for Myc mediates its functions as a specific transcriptional activator and a transforming protein. Mad and Mxi1 proteins both heterodimerize with Max and compete with each other for limiting amounts of Max. Transcriptional activation by Myc can be suppressed by increasing the amount of Mad or Mxi1. This report shows the expression pattern of these Myc related factors at the mRNA level in a small cell lung cancer (SCLC) cell line (GLC4) which is characterized by c-myc amplification and strong constitutive c-myc overexpression. We found these genes transcriptionally active but uninfluenced from high c-myc transcription. Max was constantly transcribed at a relatively low level during cell cycle progression. Mad and mxi1 mRNA was at a surprisingly high level in proliferating cells. Mad was further upregulated and mxi1 was downregulated to basal levels during serum starvation of the cells. We further analyzed the activity of c-fos, c-jun, c-myb and nm23 which are described to be involved in c-myc transcriptional activation, c-jun and c-fos were not constitutively activated and can be excluded as regulators. High steady state c-myc in contrast influences the serum stimulated transient activation mechanism of these two genes. We identified high copy number nm23 mRNA whose role as a putative c-myc transcriptional activator is under investigation. Our results indicate that constitutive overexpression of c-myc does not require the activity of the nuclear oncogenes tested and that the m-RNA expression pattern of functionally related proteins is not influenced.
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PMID:Coexpression pattern of c-myc associated genes in a small cell lung cancer cell line with high steady state c-myc transcription. 765 39


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