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

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

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 role of Ca2+ and Zn2+ in the initiation of DNA synthesis in NIH 3T3 fibroblasts and c-Ha-ras(val-12) oncoprotein-expressing (NIH 3T3) cells has been studied. Entrapment of the Ca2+ chelator, BAPTA (30 microM), into the cells totally blocked a serum-induced rise in cytosolic free Ca2+ ([Ca2+]i) as determined with fura-2. Serum starvation for 24 h considerably reduced DNA synthesis in control NIH 3T3 fibroblasts. BAPTA treatment reduced serum-induced DNA synthesis and totally inhibited platelet-derived growth factor-induced DNA synthesis in these cells. DNA synthesis of the c-Ha-ras(val-12)-expressing fibroblasts was little affected by serum starvation and unaffected by entrapment of BAPTA into the cells. Intracellular Zn2+ was measured using the fluorescent probe TSQ in intact cells. As determined using image analysis the TSQ fluorescence was distributed throughout the cytoplasm and concentrated around the nucleus. The permeable Zn2+ chelator, TPEN, at a concentration of 10 microM, caused a maximal reduction in TSQ-available Zn2+. This concentration of TPEN totally blocked DNA synthesis both in control and c-Ha-ras(val-12)-expressing fibroblasts. Upon addition of 11 microM Zn2+ DNA synthesis was restored even after TPEN addition. [3H]Thymidine incorporation itself was also sensitive to TPEN treatment. The results suggest that c-Ha-ras(val-12)-induced proliferation is independent of changes in [Ca2+]i. A specific role of Zn2+ in c-Ha-ras-induced proliferation is unlikely since ras-expressing and control cells reacted similarly to Zn2+ deprivation. There seems to be a constant requirement for the presence of Zn2+ in cell proliferation.
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PMID:Ca2+ and Zn2+ dependence of DNA synthesis in untransformed and in Ha-ras(val-12)-expressing NIH 3T3 cells. 835 24

Cervical carcinoma-associated human papillomavirus type 16 (HPV16) encodes E6 and E7 oncoproteins which inactivate p53 and Rb, respectively, but these interactions are not sufficient to account for the oncogenic potential of the virus. Several viral promoters were shown to be regulated by E6 and E7. To identify genes as cellular targets of the HPV16 early proteins, we transfected a new HPV-negative and p53-mutated cervical carcinoma-derived cell line with either the HPV16 full-length genome or the HPV16 E6 gene. HPV16 clones but not 16E6 clones showed a decreased doubling time that was not related to the viral DNA and mRNA patterns. In exponentially growing cells as well as in cells synchronized by serum starvation, expression of the E6 gene was associated with upregulation of the c-fos and c-jun proto-oncogenes and with downregulation of the c-Ha-ras gene. Furthermore, a viral gene other than E6 may be involved in downregulation of p53 because a reduced mRNA level at the G1/S transition was observed only in HPV16-cells. The present study on natural host cells indicates p53-independent transcriptional modulations of cell cycle regulatory genes related to HPV16 E6 and E7 expression.
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PMID:The early HPV16 proteins can regulate mRNA levels of cell cycle genes in human cervical carcinoma cells by p53-independent mechanisms. 958 83

The apoptosis-resistant phenotype of cloned high-metastatic A11 and low-metastatic P29 cells isolated from Lewis lung carcinoma was compared. The results showed that A11 cells were more resistant to apoptosis induced by microenvironmental stresses such as serum starvation, glucose deprivation and hypoxia than P29 cells as judged by viability, DNA laddering, and chromatin condensation and fragmentation. Both cell lines were insensitive to tumor necrosis factor-alpha-mediated apoptosis. P29 cells expressed a much higher level of Fas antigen on the cell surface than A11 cells. However, both cell lines were also insensitive to Fas-mediated apoptosis. The apoptosis resistant phenotype of A11 cells was associated with the expression level of caspase-3, but not with those of Bcl-2, Bcl-X(L) Bax, p27Kip1 and DAP kinase. There was no difference between A11 and P29 cells in the expression of E-cadherin, the adhesiveness to the extracellular matrix components or the expression levels of metastasis-associated genes such as c-Ha-ras, c-jun, p53 and nm23. Furthermore, A11 cells exhibited lower motile and invasive abilities than P29 cells. These results suggest that the apoptosis-resistant phenotype is an important factor for determining the metastatic ability of A11 cells. Supporting this, P29 cells became more apoptosis-resistant after treatment of the cells with dimethylsulfoxide which is reported to enhance the experimental metastatic potential of the cells.
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PMID:Resistance to apoptosis induced by microenvironmental stresses is correlated with metastatic potential in Lewis lung carcinoma. 1065 7

The antiproliferative effect of human bcl-2 gene transferred to E1A + c-Ha-ras-transformed rat embryo fibroblasts, which are characterized by the absence of cell cycle checkpoints after damage and by a high proapoptotic sensitivity was studied. Ionizing irradiation, adriamycin treatment, and serum starvation were shown to induce G1/S arrest in E1A + c-Ha-ras-transformants. Bcl-2 antiproliferative effect in E1A + c-Ha-ras-transformants was not associated with alterations in Cdk2, cyclin E and A contents. G1/S arrest following irradiation or serum starvation was accompanied by a decrease in kinase activity associated with cyclin E-cdk2, whereas G1/S arrest in tetraploid subpopulation after adriamycin treatment did not correlate with a decrease in cyclin E-associated kinase activity. Cyclin A-associated kinase activity did not decrease after any used treatment. Transfection of bcl-2 in E1A + c-Ha-ras-transformants resulted in elevated expression of cyclin-cdk complexes inhibitor p21/Waf-1, but not p27/Kip. Damaging agents caused p21/Waf-1 and p27/Kip accumulation, but bcl-2 overexpression did not restore functions of these inhibitors, since p21/Waf-1 and p27/Kip were unable to suppress cyclin-cdk complexes activity after damage. These results suggest that bcl-2 transfection in E1A + c-Ha-ras-transformants is likely to result in irradiation- or serum starvation-induced G1/S arrest accomplished by a selective decrease in cyclin E-associated kinase activity. Adriamycin-induced G1/S arrest seems to be realized via cyclin-cdk complexes activity-independent way involving antiproliferative targets downstream of cyclin E-cdk2 and cyclin A-cdk2 complexes.
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PMID:[Changes in the activity of cyclin-kinase complexes governing cell transition from G1 phase to DNA replication phase in E1A + c-Ha-ras transformants transfected with the bcl-2 gene]. 1272 79

We have studied the ability of ERK1,2, JNK1,2 and p38 kinases to be regulated after serum deprivation in E1A + E1B-19 kDa- and E1A + E1A + c-Ha-ras-transformed rat embryo fibroblasts. It was demonstrated that oncogene transformation resulted in an increase of total kinase content independently of the type of complementing oncogene. However, for ERK1,2 kinases phosphorylation was found to depend on the type of complementing oncogene. Besides, unusual biphasic character for ERK1,2 kinases phosphorylation was checked in control fibroblasts REF52 and in transformed E1A + E1B-19 kDa cells, which undergo G1/S arrest after a 24 h serum starvation. According to the immunoblotting data, phosphorylated forms of ERK1,2 kinases are not detected after 15-30 min of serum deprivation, but their content is restored up to the control level within several hours. At the same time, the level of ERK1,2 phosphorylation in E1A + c-Ha-ras cells did not change after serum withdrawal. Besides, serum deprivation did not lead to significant changes in the level of phosphorylation of both type stress kinases--JNK2 and p38 in all types of studied cells. We discuss possible mechanisms of biphasic alteration in ERK1,2 phosphorylation level under condition of serum deprivation of REF52 cells and E1A + E1B-19 kDa-transformed fibroblasts, able to be arrested in G1 phase.
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PMID:[MAP-kinase cascade analysis in transformed cell with different abilities to make G1/S block under serum starvation]. 1452 Oct 57

E1A + c-Ha-ras-transformants overexpressing bcl-2 oncogene are able to be arrested at the G1/S boundary of the cell cycle after DNA damage and upon serum starvation, this cell cycle blockage being accompanied by a decrease in the activity of cyclin E--Cdk2 complexes. Roscovitine-induced inhibition of cyclin-dependent kinases (Cdks) activity does not result in the G1/S arrest of E1A + c-Ha-ras + bcl-2-transformants. Roscovitine treatment causes an accumulation of G2/M cells, mainly at the expense of mitotic cells. However, the expression of Bcl-2 oncoproducts does not re-establish the regulation of mitotic events broken by introduction of E1A and c-Ha-ras oncogenes in normal cells, as revealed by the treatment of E1A + c-Ha-ras + bcl-2-transformants with nocodazole inducing mitotic arrest in normal cells. In spite of the elevated expression of antiapoptotic bcl-2 gene in transformants, nocodazole treatment results in mass apoptotic death preceded by polyploidy. Roscovitine also induces apoptosis with no polyploid cell accumulation being observed. Inhibition of Cdks activity with Roscovitine, as well as violation of microtubule depolymerization with nocodazole result in the apoptotic death in the tested cell lines sensitive (E1A + c-Ha-ras) and resistant (E1A + c-Ha-ras + bcl-2) to damaging agents. Thus, the application of Roscovitine, a specific inhibitor of Cdks, suggests that the decrease in Cdks activity in E1A + c-Ha-ras + bcl-2-transformants is not likely to be responsible for G1/S cell cycle arrest realization after damaging influences. Moreover, an antiproliferative effect of Bcl-2 in E1A + c-Ha-ras-transformants is restricted by restoration of cell cycle events at G1/S and G2/M boundaries, and does not concern the program of mitotic events regulation.
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PMID:[Antiproliferative effect of bcl-2 gene does not concern the control of mitotic events]. 1521 71

Introduction of bcl-2 gene in EIA + c-Ha-ras-transformed rat embryo fibroblasts, which are unable to be arrested after damaging influences and possess high proapoptotic sensitivity, results not only in suppression of cell death but also in re-establishment of cell cycle block following DNA damage and serum starvation. Flow cytometry showed that E1A + c-Ha-ras + bcl-2-transformants treated with DNA-intercalator adriamycin are capable of being arrested at G1/S boundary for a long time (for less than 5 days). According to the growth curve data, the number of Bcl-2-overexpressing cells remanins constant for a week of cultivation with adriamycin. Clonogenic efficacy of E1A + c-Ha-ras + bcl-2-cells is brought to no already in 16 h after adriamycin addition. Apoptotic death, revealed by oligonucleosomic fragmentation of DNA, as well as cell death, occurring due to mitotic catastrophe, after adriamycin treatment are almost absent in Bcl-2-overexpressing transformants, as compared with parental E1A + c-Ha-ras-transformants. Bcl-2 introduction in E1A + c-Ha-ras-transformants is accompanied by a rise of SA beta-Gal (Senescence Associated beta-Galactosidase) activity, which is commonly considered to be a marker of cell senescence. Adriamycin treatment of E1A + c-Ha-ras + bcl-2-transformants results in a much higher rise in SA beta-Gal activity, as compared with untreated cells. Co-immunoprecipitation experiments demonstrated the introduction of Bcl-2 to result in formation of Bcl-2 complexes with early region E1A oncoproducts, which are thought to be responsible for proapoptotic susceptibility of E1A-expressing transformants. The data obtained lead to suggestion that bcl-2 transfer to E1A + c-Ha-ras-transformants may induce a switch from the cell death program on the program of senescence after DNA damage, due, presumably, to Bcl-2 interaction with the apoptosis activator the viral oncoprotein E1A.
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PMID:[Antiapoptotic oncogene bcl-2 induces a program of senescence in E1A + c-Ha-ras-transformants treated with adriamycin]. 1671 90