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

Proliferation of a murine macrophage cell line (BAC1.2F5) in response to colony-stimulating factor 1 (CSF-1) is inhibited by prostaglandin E2 (PGE2)-mediated elevation of intracellular cyclic AMP (cAMP). When BAC1.2F5 cells were growth arrested in early G1 by CSF-1 starvation and stimulated to synchronously enter the cell cycle by readdition of growth factor, PGE2 inhibited [3H]thymidine incorporation when added before mid-G1, but its addition at later times did not block the onset of S phase. Reversible cell cycle arrest mediated by a cAMP analog required the presence of CSF-1 for cells to initiate DNA synthesis, whereas cells released from an aphidicolin block at the G1/S boundary entered S phase in the absence of CSF-1. PGE2 or cAMP analogs did not block the initial induction of c-myc mRNA by CSF-1 but abolished the CSF-1-dependent expression of c-myc mRNA in the mid-G1 stage of the cell cycle. The cAMP-mediated reduction in c-myc RNA levels was due to decreased c-myc transcription. However, CSF-1-dependent BAC1.2F5 clones infected with a c-myc retrovirus were growth arrested by cAMP analogs despite constitutive c-myc expression. Therefore, the reduction of endogenous c-myc expression by cAMP is neither necessary nor sufficient for growth inhibition.
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PMID:Macrophage growth arrest by cyclic AMP defines a distinct checkpoint in the mid-G1 stage of the cell cycle and overrides constitutive c-myc expression. 137 14

We have recently reported that prostaglandin D2 (PGD2) specifically elevates the intracellular cyclic AMP (cAMP) level in a fibroblastic cell line derived from bovine embryonic trachea (EBTr) (K. Sugama, T. Tanaka, H. Yokohama, M. Negishi, H. Hayashi, S. Ito, and O. Hayaishi, Biochim. Biophys. Acta, 1011: 75-80, 1989). Since the in vitro and in vivo inhibitory effects of PGD2 on cell growth are attributed to the dehydrate product 9-deoxy-delta 9,12-13,14-dihydro-PGD2 (delta 12-PGJ2), the role of cAMP as a mediator of PGD2-induced cell growth has been questioned. In this study we investigated the effects of PGD2 on cAMP level, DNA synthesis, and c-myc expression using EBTr cells growth-arrested by serum starvation. Quiescent EBTr cells synchronously resumed [3H]thymidine incorporation at 12 h after the addition of serum, an incorporation which ended at 21 h. PGD2 at 1 microM inhibited approximately 30% incorporation without any delay of initiation, and it also caused a rapid increase in the cAMP level at a maximum of 10 min. The inhibition of [3H]thymidine incorporation was increased 40-45% by 5 microM 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. The expression of c-myc mRNA induced by serum at 1-4 h was also inhibited by PGD2. Time-course studies support the association between the reduction of c-myc expression and the successive inhibition of DNA synthesis by PGD2. The dose dependency of PGD2 for these three processes correlated well with each other, and the effects were evident at as low as 10 nM and specific for PGD2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic AMP-mediated inhibition of cell growth by prostaglandin D2 in a fibroblastic cell line (EBTr). 170 11

We have examined and quantitated the expression of c-myc protein in two untransformed fibroblast cell lines, murine Swiss 3T3 and human MRC-5, c-myc protein is not detectable in quiescent cells, but it is rapidly induced upon mitogenic stimulation. Peak expression is seen about 3-5 h after serum stimulation, and corresponds to about 3-6000 molecules per cell (mpc). Thereafter, levels fall back to a quiescent level in confluent fibroblasts, but remain elevated at 1-3000 mpc in subconfluent cells. The c-myc protein is phosphorylated and has the same size and short half-life as seen in tumour cells. Removal of serum growth factors from the culture medium causes very rapid loss of the c-myc protein from all cells, irrespective of their positions in the cell cycle. Thus, c-myc expression is continuously dependent upon the presence of mitogens. However, no single tested mitogen is obligatory for maintenance of expression in proliferating cells. Growth arrest of cells, either by metabolite starvation or by drugs which inhibit DNA synthesis, does not affect expression of the c-myc protein, which remains completely dependent upon the presence of mitogens. These data are consistent with the c-myc protein's having a continuous role in proliferating cells as an intracellular integrator of growth regulatory signalling pathways.
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PMID:c-myc protein expression in untransformed fibroblasts. 205 58

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

We have compared the nucleosomal organization of c-Ha-rasVal 12 oncogene-transformed NIH-3T3 fibroblasts with that of normal fibroblasts by using micrococcal nuclease (MNase) as a probe for the chromatin structure. The bulk chromatin from asynchronously and exponentially growing ras-transformed cells was much more sensitive to MNase digestion than chromatin from the normal cells. Southern hybridization analyses of the MNase digests with probes specific for the ornithine decarboxylase (odc) and c-myc genes showed that the coding and/or 3' end regions of these growth-inducible genes carry a nucleosomal organization both in ras-transformed and normal cells. Studies with cells synchronized by serum starvation showed that in both cell lines the nucleosomal organization of chromatin is relatively condensed at the quiescent state, becomes highly decondensed during the late G1 phase of the cell cycle, and starts again to condense during the S phase. However, in ras-transformed cells the decondensation state stayed much longer than in normal cells. Moreover, irrespective of the phase of the cell cycle the bulk chromatin as well as that of the odc and c-myc genes was more sensitive to MNase digestion in the ras-transformed cell than in the normal fibroblast. Decondensation of the chromatin was also observed in the normal c-Ha-ras protooncogene-transfected cells, but to a lesser extent than in the mutant ras-transformed cells. Whether the increased degree of chromatin decondensation plays a regulatory role in the increased expression of many growth-related genes in the ras-transformed cells remains an interesting object of further study.
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PMID:c-Ha-rasVal 12 oncogene-transformed NIH-3T3 fibroblasts display more decondensed nucleosomal organization than normal fibroblasts. 219 41

A plasmid containing the CAT (chloramphenicolacetyltransferase) gene fused to the 5' adjacent sequences and first exon of the human c-myc gene was stably transfected into NIH3T3 cells. Single cell clones were grown and CAT activity was measured after serum starvation and stimulation. CAT activity of the hybrid construct remained unchanged in serum-deprived and serum-stimulated cells. In contrast the steady-state RNA level of the endogenous mouse c-myc gene was strongly elevated upon serum stimulation. The bona fide usage of the human c-myc promoter P1/P2 in mouse cells carrying the hybrid gene was revealed by S1 analysis.
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PMID:A stably transfected c-myc cat hybrid gene is not regulated by serum in NIH3T3 cells. 305 27

Previous work has shown that the members of the myc protooncogene family are differentially regulated during murine development (Zimmerman et al., 1986). In this study, we have used the F9 mouse teratocarcinoma cell line to investigate the expression of two members of this family, the N- and c-myc genes. We demonstrate here that both N-myc and c-myc RNAs are unstable in these cells, but that they are clearly differentially regulated during a variety of cellular processes. Following retinoic acid addition, N-myc expression declines but then returns to initial levels as the cells undergo endodermal differentiation. c-myc RNA levels decrease more slowly and remain low in the differentiated cells. Additionally, we find that serum starvation and serum stimulation, treatments that alter c-myc RNA levels, do not have a significant effect on N-myc expression. These results provide further support for a role of c-myc expression in growth control but demonstrate that N-myc levels are not correlated with proliferative state of the cell.
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PMID:Differential regulation of N-myc and c-myc expression in F9 teratocarcinoma cells. 306 Aug 4

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

We examined the expression of N-myc, c-myc, and c-src in four embryonic carcinoma (EC) cell lines during different states of cell growth and following induction of in vitro differentiation. N-myc mRNA was detected in undifferentiated cells of four EC cell lines (PCC7, PCC3, PCC4, F9) neither of which showed N-myc gene amplification. No N-myc transcripts could be detected in mRNA prepared from a murine neuroblastoma cell line and from a murine fibroblast line. The level of N-myc mRNA decreased by 85% when PCC7 EC cells were induced by retinoic acid and cAMP treatment to form nerve-like cells. Six days after induction, the PCC7 cells changed into aggregates of neurofilament positive cells with massive neurite outgrowths. At this stage DNA replication had been reduced by more than 95%. The decreased N-myc expression in induced PCC7 cells was parallelled by 300-500% increase in c-src expression. Slowing of cell multiplication by serum starvation, on the other hand, did not affect the level of N-myc or c-src mRNA levels in PCC7 cells. C-myc was expressed in all EC lines except PCC7, which surprisingly did not express c-myc even at an exponential rate of proliferation. Chemical induction of F9 EC cells to form visceral endoderm or parietal endoderm resulted in markedly reduced (85%) levels of N-myc transcripts. A similar decline in c-myc expression was found in differentiated F9 cells. No c-src transcripts were detected in proliferating or differentiated F9 cells. These results suggest that N-myc may be expressed not only in neural development, but also in very early, undetermined embryonic cells. The activation of c-src expression when PCC7 EC cells differentiate into nerve-like cells shows that the pattern of proto-oncogene expression may change during a differentiation process, some proto-oncogenes increasing, others decreasing their representation in the mRNA pool.
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PMID:N-myc and c-src genes are differentially regulated in PCC7 embryonal carcinoma cells undergoing neuronal differentiation. 370 Apr 83


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