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  • 1
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 152 (1992), S. 177-184 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We have examined the regulation of the proliferating cell nuclear antigen gene (PCNA) in a hamster fibroblast cell line (tk-ts 13) which is temperature sensitive for growth. These tk-ts 13 cells, at the restrictive temperature, are growth arrested in the G1 phase of the cell cycle. The cells were stably transfected with a full length human PCNA gene, and the resulting cell lines (K525 cells) were analyzed. We find that, in growth arrested K525 cells, a cryptopromoter is activated in the transfected human PCNA gene. The cryptopromoter resides in intron 4 which is necessary for proper regulation of the PCNA gene. Removal of this intron leads to increased expression of PCNA in cells which have entered the Go state. An Alu sequence residing in intron 4 is implicated as the promoter element which is active during growth arrest. © 1992 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The interaction of insulin-like growth factors (IGFs) with the IGF-1 receptor is an important step in the control of cell proliferation and development. In particular, IGF-1 and IGF-2 are key regulators of central nervous system development, and may modulate the growth of glial tumors. We have investigated the growth factor regulation of the human glioblastoma cell line T98G. These cells growth arrested in serum-free medium at 34°C, despite their secretion of substantial amounts of bioactive IGF-1. To be stimulated to divide, growth-arrested cells required the addition of platelet-derived growth factor (PDGF) or its equivalent, 1% serum. Cell proliferation in serum-free medium could also be obtained by shifting the cells to a temperature of 39.6°C. Treatment of growth-arrested cells with PDGF or temperature shift was accompanied by a transient increase in the expression of the mRNA for the IGF-1 receptor. Transfection with a plasmid constitutively expressing the full cDNA for the human IGF-1 receptor allowed autonomous growth in serum-free medium at 34°C. By contrast, growth induction by growth factors or temperature shift was abrogated by transfection of the cells with a plasmid expressing a 300 bp segment of mRNA antisense to the IGF-1 receptor mRNA. Cloning in soft agar was also inhibited by expression of antisense IGF-1 receptor mRNA. These results demonstrate that the IGF-1 receptor is strictly required for the growth of T98G glioblastoma cells. Moreover, the autocrine interaction of IGF-1 with its receptor regulates both autonomous and anchorage-independent growth of these cells. © 1994 wiley-Liss, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The addition of dexamethasone (dex) to human fibroblast cultures has been found to elicit enhanced proliferation. This enhancement is manifested by an increase in the initial growth rate, saturation density, and proliferative life span of WI-38 fibroblast cultures grown in the presence of dex. We examined the acute effects of dex on a number of growth-related genes in WI-38 cells. Our results show a decrease in the level of the cyclin-dependent kinase inhibitor p21Waf1/Cip1/Sdi1 in response to dex. In addition, the level of the insulin-like growth factor type 1 receptor (IGF-1R) is increased in dex-treated cells. These changes are correlated with changes in the activity of the p21Waf1/Cip1/Sdi1 and IGF-1R promoters. The results presented in this report suggest that dex may delay growth arrest in response to contact inhibition, as well as during cellular senescence. Thus, dex may act at multiple levels to enhance cellular proliferation in WI-38 cells: first, to decrease the level of an inhibitor of cell-cycle progression, and second, to increase the sensitivity of WI-38 cells to the proliferative effects of IGF-1. These acute effects may cooperate with other, as yet uncharacterized effects, to result in the enhanced proliferation seen in the presence of dex. J. Cell. Physiol. 177:396-401, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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