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

Expression of the oncogenes c-myc, c-raski, and p53 is studied in normal primary mouse cultures and in two adenovirus-transformed mouse cell lines. In all cases oncogene expression is measured in cells arrested in G1 (or G0 for primary cells) by serum starvation and at different times after cell cycle traverse is stimulated by addition of high serum. For primary mouse cells, c-myc mRNA levels are found to increase four- to six-fold within 1 h of serum addition and then decline by 4 h to nearly the level observed in serum-starved cells. This level is maintained throughout the remainder of the cell cycle. The early induction of c-myc is dependent on serum concentration and is independent of cell density. These results confirm and extend previous observations for primary cells. By contrast, expression of c-raski does not vary at all through the cell cycle and p53 increases with time after mitogenic stimulation. In the adenovirus-transformed cell lines, the regulation of expression of c-myc with respect to the cell cycle is altered. There is an increase in c-myc in S phase cells which is dependent on cell density and the early induction in response to serum addition as seen in primary cells is absent. Expressions of c-raski and p53 are found to show similar profiles to those observed for primary cells.
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PMID:Altered regulation of c-myc expression in adenovirus-transformed cells. 380 68

The highly increased fibrinolytic activity of HeLa cells, treated with the tumor promoting phorbol ester, phorbol myristate acetate (PMA), correlates with equally increased levels of tissue-type plasminogen activator (t-PA) antigen in the conditioned media of these cells and concomitantly increased steady state levels of t-PA-specific mRNA. The effect of PMA on t-PA mRNA levels is completely blocked by pretreatment of the cells with the inhibitor of translation, cycloheximide, indicating that it requires the biosynthesis of at least one protein intermediate. In contrast, mRNA of the oncogene product c-myc can be induced for a brief period immediately following serum starvation in the presence and absence of PMA, and in the presence of cycloheximide. Our results suggest that increased t-PA biosynthesis in HeLa cells, probably through an increased rate of translation of the t-PA gene, forms part of the "late" events of the pleiotropic response to tumor promoters.
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PMID:Induction of fibrinolytic activity in HeLa cells by phorbol myristate acetate. Tissue-type plasminogen activator antigen and mRNA augmentation require intermediate protein biosynthesis. 403 26

Previous studies in human myeloid leukemia cells (HL-60, U-937, THP-1) suggested an involvement of the c-myc gene in the control of mutually exclusive pathways, such as retrodifferentiation and cell death. Treatment of U-937 cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) which is associated with the induction of a monocytic differentiation program and growth arrest, revealed an initial up-regulation of c-myc, c-max, and mxi1 mRNAs after 1-6 h. Thereafter expression of these genes significantly declined to barely detectable levels when the cells ceased to grow after 12-24 h of TPA treatment. Between 7 and 11 days of TPA-induced G0/G1 cell cycle arrest, expression of the c-max and mxi1 genes continuously increased up to 8-fold until 32 days and declined to control levels when the cells regained proliferative capacity by 36 days. In contrast, c-myc mRNAs remained down-regulated during periods of growth arrest and increased only during re-entry into the cell cycle after 36 days. This effect is consistent with a retrodifferentiation process, whereby previously differentiated cells revert back to the undifferentiated phenotype and re-enter the cell cycle. Different results were obtained during serum starvation-induced cell death of U-937 cells. After 48-72 h of serum-starvation, expression of the c-myc and c-max genes were significantly down-regulated by 4-fold and 3-fold, respectively, while there was little, if any, change in mxi1 mRNA levels. Analysis of cell death in serum-starved U-937 cells demonstrated progressively increasing DNA fragmentation reaching 45.4% +/- 0.9% after 72 h. Synchronization of proliferating U-937 cells throughout distinct phases of the cell cycle exhibited little, if any, change in c-myc, c-max and mxi1 mRNAs. Furthermore, like c-myc, c-max and mxi1 mRNA transcripts appeared to be regulated primarily by post-transcriptional mechanisms, and c-max and mxi1 half-lives exceeded 4 h in contrast to < 60 min for the c-myc gene. Taken together, these findings suggested differential regulation and inverse expression levels of c-myc compared to c-max and mxi1 during differentiation, retrodifferentiation and cell death.
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PMID:Differential expression of c-myc, max and mxi1 in human myeloid leukemia cells during retrodifferentiation and cell death. 750 Jun 45

Genes encoding cdk1 (p34cdc2), cyclin A, cyclin B, and the tumor suppressor gene Rb are fundamental regulators of cell cycle progression which associate as a complex with the transcription factor E2F. Expression of many of these proteins has previously been shown to be repressed by okadaic acid, a specific inhibitor of protein phosphatases 1/2A (PP1/PP2A), resulting in growth arrest in nontransformed but immortalized cells. We have investigated levels of mRNA encoding cdk1 (p34cdc2), cyclin A, cyclin B, Rb, GAPDH, c-myc, and histone H4 genes for sensitivity to okadaic acid in HeLa cells to determine if transformation altered their regulation. Serum starvation slowed growth and diminished mRNA levels for all genes tested except c-myc and GAPDH. When starved cells were subsequently exposed to 19 nM okadaic acid or refed 10% serum, mRNA levels of cyclin A, cyclin B, cdk1, and Rb dramatically increased while mRNA levels for c-myc and GAPDH were largely unaffected. Histone H4 mRNA levels and the rate of DNA synthesis were greatly enhanced by serum addition but not affected appreciably by okadaic acid. Okadaic acid was also effective in blocking proliferation of exponentially growing HeLa cells at G2/M and S phase. Despite the cell cycle phase-specific block, elevated mRNA levels for cdk1, cyclin A, cyclin B, Rb, and suppression of H4 mRNA levels were detected and persisted for at least 12 hr following okadaic acid removal. The results demonstrate that cell cycle progression is blocked and several cell cycle regulatory genes, encoding transcription factor E2F-associated proteins, experience elevation of mRNA levels through mechanisms sensitive to okadaic acid likely through a PP1/PP2A-sensitive mechanism. Data from transformed cells contrast with data from immortalized but nontransformed cells in which okadaic acid also blocks cell cycle progression during G2/M phase but suppresses expression of these genes. Such contrasts may be correlated with reduced growth factor dependence and transformation.
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PMID:Selective induction of cell cycle regulatory genes cdk1 (p34cdc2), cyclins A/B, and the tumor suppressor gene Rb in transformed cells by okadaic acid. 762 88

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 product of the c-myc proto-oncogene (c-Myc) is involved in the control of cell proliferation, differentiation, and apoptosis. It acts as a transcription factor that recognizes the CACGTG motif. This sequence has also been found in the glucose-responsive elements of genes involved in the control of liver glycolysis and lipogenesis. To determine whether c-Myc can regulate hepatic carbohydrate metabolism in vivo, transgenic mice that overexpress c-myc under control of the P-enolpyruvate carboxykinase (PEPCK) gene promoter have been generated. These mice showed a threefold increase in c-Myc protein in liver nuclei. Hepatocytes from transgenic mice were normal and did not acquire the fetal phenotype. However, transgenic mice showed higher levels (threefold) of L-type pyruvate kinase mRNA and enzyme activity than control mice. The increase in pyruvate kinase activity led to a three- to fivefold increase in liver lactate content and a fivefold induction of lactate production by hepatocytes in primary culture. The expression of the 6-phosphofructo-2-kinase gene was also increased in the liver of these transgenic mice. The induction of hepatic glycolysis was related with an increase in the expression (about fourfold) and activity (about threefold) of liver glucokinase, whereas no change was noted in hexokinase-I. This change in glucokinase activity led to an increase in both glucose 6-phosphate and glycogen contents in the liver of transgenic mice. The expression of the liver-specific glucose transporter GLUT2 was also increased in transgenic mice, whereas no change was noted in the mRNA concentration of GLUT1. Furthermore, the changes of liver glucose metabolism led to a marked reduction of blood glucose (25%) and insulin (40%) concentrations in starvation, whereas the fall in both was only 10% in fed mice. Thus, liver glucose metabolism could determine the blood glucose and insulin set points in the transgenic mice. All these results indicated that the increase in c-Myc protein was able to induce liver glucose utilization and accumulation, and suggested that c-Myc transcription factor is involved in the control in vivo of liver carbohydrate metabolism.
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PMID:Evidence from transgenic mice that myc regulates hepatic glycolysis. 764 6

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

Transcription of the ribosomal RNA genes by RNA polymerase I is tightly coordinated with the rate of cell growth. The RNA polymerase I transcription factor, UBF, activates transcription by binding to elements within the promoter and enhancer elements within the intergenic spacer but is not required for basal transcription. To assess the role of UBF in modulating ribosomal DNA transcription, we studied its expression in NIH3T6 fibroblasts when transcription was repressed in response to serum starvation and stimulated following refeeding. Our results demonstrate a correlation between the amounts of UBF protein and the rates of ribosomal DNA transcription in quiescent and serum-stimulated cells. Nuclear run-on assays and Northern blot analyses demonstrated that the UBF gene was a primary response gene, exhibiting characteristics similar to those of c-myc and SRF. These results suggest that the regulation of transcription of the UBF gene by polymerase II represents a pathway by which cells modulate transcription by RNA polymerase I.
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PMID:The RNA polymerase I transcription factor UBF is the product of a primary response gene. 787 78

Oral vanadate administration has been demonstrated to normalize blood glucose levels in ob/ob and db/db mice and streptozotocin (STZ) diabetic rats. The exact mechanism of this vanadate effect is uncertain, since there are no consistent effects on the insulin receptor tyrosine kinase activity or phosphotyrosine phosphatase activity. We have therefore studied the postreceptor actions of vanadate, focusing our attention on the steady-state levels of mRNA of enzymes involved in carbohydrate metabolism. When compared with their lean (ob/+) controls, the livers of ob/ob mice exhibited an approximately 90% reduction in the levels of phosphoenolpyruvate carboxykinase (PEPCK) mRNA and twofold to fivefold higher levels of the mRNAs for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the "liver beta-cell" glucose transporter (GLUT2), and the proto-oncogene c-myc. Administration of sodium vanadate (0.25 mg/mL) in the drinking water of ob/ob mice over a 45-day period resulted in a near normalization of blood glucose and increased PEPCK mRNA levels more than ninefold. Starvation of the ob/ob mice for 24 to 48 hours also increased PEPCK mRNA levels by fourfold to 15-fold. Vanadate treatment did not alter mRNA levels of any other proteins studied and had no effect on PEPCK mRNA in ob/+ mice. However, 1 to 100 mumol/L vanadate produced a concentration-dependent increase in PEPCK mRNA levels in an H35 hepatoma cell line, an effect opposite to the suppression of PEPCK mRNA produced by insulin. In summary, hyperglycemia in the ob/ob mouse is characterized by decreased expression of PEPCK and increased expression of GAPDH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vanadate normalizes hyperglycemia and phosphoenolpyruvate carboxykinase mRNA levels in ob/ob mice. 796 88

Deregulated expression of the c-myc proto-oncogene can lead to apoptosis under certain physiological conditions. By introducing a conditionally active Myc allele into primary embryo fibroblasts null for p53, and into fibroblasts without endogenous p53 expression but ectopically expressing a temperature-sensitive p53 allele, we show that expression of wild-type p53 is required for susceptibility to Myc-mediated apoptosis. Although ectopic expression of wild-type p53 blocked cells in the G1 phase of the cell cycle, G1 arrest by isoleucine starvation, in a manner independent of p53, did not confer susceptibility to apoptosis. Thus, growth arrest per se is not sufficient to induce Myc-mediated apoptosis; instead, a property intrinsic to p53 is specifically required. Moreover, apoptosis did not require induction of p53 target proteins, including the cyclin-dependent kinase inhibitor p21waf1/cip1. Therefore, the role of p53 in apoptosis may be distinct from its role in cell cycle arrest.
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PMID:Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1. 799 20


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