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  • gene expression  (2)
  • ODC  (1)
  • WI-38 cells  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 75 (1987), S. 61-70 
    ISSN: 1573-4919
    Keywords: gene expression ; development ; tissue-specific expression ; cell cycle-dependent genes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract 4F1, 2A9 and 2F1 represent three of a number of cDNA sequences which have been identified because their cognate RNAs markedly increase when quiescent cells in culture are stimulated with serum. Studies using a variety of cell culture systems have shown that the expression of these genes is modulated by various growth factors and mitogens and thus such genes are considered to be ‘growth-associated.’ Thus far, little information has been obtained with these in vitro systems about the function of these genes. In an attempt to begin to elucidate the role of these genes (if any) in the physiology of the normal cell, we have analyzed the levels of 4F1, 2A9 and 2F1 transcripts in a variety of differentiated organs and tissues of adult and fetal rats. Our results show that each of these growth-associated genes exhibits its own unique pattern of expression, unrelated to the proliferative activity of the tissue. These data suggest that these genes most likely do have specific functions in normal tissue in addition to their role in the induction of DNA synthesis in quiescent cells in culture.
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  • 2
    ISSN: 0730-2312
    Keywords: c-jun ; junD ; cardiomyopathy ; myosin ; gene expression ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The proto-oncogenes c-jun and junD are closely related transcriptional factors with opposing actions on cell growth and division. Expression of c-jun rapidly increases as cells enter the cell cycle. Levels of c-jun are also increased in the early stages of experimental cardiac hypertrophy and failure but expression decreases with time. In contrast, junD accumulates in quiescent cells. Expression in end-stage cardiomyopathy has not been studied. Steady-state levels of c-jun and junD mRNA were determined in failing human myocardium (obtained at the time of cardiac transplantation) and in control myocardium from patients who died of noncardiac causes. Relative expression was normalized for glyceraldehyde-3-phosphate dehydrogenase expression. Levels of junD were almost four-fold depressed in myocardium from myopathic hearts (2.1 ± 0.27, × ± SE; n = 20) vs. the controls (7.7 ± 1.1; n = 3). Levels of c-jun were similar in both myopathic and control hearts. Relative expression of beta-myosin heavy chain was the same in both myopathic and control hearts. Levels of junD were still found to be depressed in the myopathic hearts after normalization for myosin heavy chain gene expression. We conclude that c-jun and junD are differentially regulated in end-stage human cardiomyopathy with expression of junD being decreased while relative levels of c-jun mRNA remain unchanged. Further studies are needed to determine the role of junD down-regulation in the development and/or maintenance of the abnormalities present in end-stage heart disease. J. Cell. Biochem. 65:245-253. © 1997 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 54 (1994), S. 405-414 
    ISSN: 0730-2312
    Keywords: competence ; progression ; G-1 ; c-Myc ; ODC ; cell cycle ; quiescence ; WI-38 cell ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: A number of cell culture model systems have been used to study the regulation of cell cycle progression at the molecular level. In this paper we describe the WI-38 cell long-term quiescence model system. By modulating the length of time that WI-38 cells are density arrested, it is possible to proportionately alter the length of the prereplicative or G-1 phase which the cell traverses after growth factor stimulation in preparation for entry into DNA synthesis. Through studies aimed at understanding the cause and molecular nature of the prolongation of the prereplicative phase, we have determined that gene expression plays an important role in establishing growth factor “competence” and that once the cell becomes “competent” there is a defined order to the molecular events that follow during the remainder of G-1. More specifically, we have determined that the prolongation represents a delay in the ability of long term quiescent cells to become fully “competent” to respond to growth factors which regulate progression through G-1 into S. This prolongation appears to occur as a result of changes during long term quiescence in the ability of immediate early G-1 specific genes (such as c-myc) to activate the expression of early G-1 specific genes (such as ornithine decarboxylase). While ODC is the first and thus far only growth associated gene identified as a target of c-myc (and the Myc/Max protein complex), it is likely that further studies in this model system will reveal other early G-1 growth regulatory genes. We anticipate that future follow-up studies in this model system will provide additional valuable information abuot the function of growth-regulatory genes in controlling growth factor responsiveness and cell cycle progression.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 59 (1995), S. 42-52 
    ISSN: 0730-2312
    Keywords: WI-38 cells ; protein tyrosine kinases ; IGF-1 receptor ; growth factors ; EGF ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We have used the WI-38 cell long-term quiescent model system to study the regulation of cell cycle progression at the molecular level. By modulating the length of time that WI-38 cells are density arrested, it is possible to proportionately alter the length of the prereplicative or G-1 phase which the cell traverses after growth factor stimulation in preparation for entry into DNA synthesis. Stimulation of long-and short-term density arrested WI-38 cells with different growth factors or higher concentrations of individual growth factors does not alter the time required by long-term cells to enter S after stimulation. However, the time during the prereplicative period for which these growth factors are needed is different. Long-term quiescent WI-38 cells require EGF to traverse the G-0/G-1 border but do not need and apparently cannot respond to IGF-1 during the first 10 h after EGF stimulation, the length of the prolongation of the prereplicative phase. This suggests that EGF stimulation of long-term quiescent WI-38 cells initiates a series of molecular events which make these cells “competent” to respond to the “progression” growth factor, IGF-1. In light of the well-established role of protein tyrosine kinases in signal transduction, we set out to identify, clone, and analyze the expression of receptor and non-receptor tyrosine kinases which potentially could play a role during the prolongation of the prereplicative phase in making the long-term quiescent WI-38 cells competent to respond to IGF-1. We obtained 49 clones representing 11 different receptor and non-receptor type protein tyrosine kinases. Analysis of expression of these clones revealed a variety of different patterns of expression. However, the most striking pattern was exhibited by IGF-1 receptor. Our results suggest that induction of IGF-1 receptor mRNA by EGF may be an important event in the establishment of competence by EGF in long-term density arrested WI-38 cells. © 1995 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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