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  • Title: Platelet-derived growth factor-induced expression of messenger RNA for the proliferating cell nuclear antigen requires a functional receptor for the insulin-like growth factor I.
    Author: Miura M, Li SW, Dumenil G, Baserga R.
    Journal: Cancer Res; 1994 May 01; 54(9):2472-7. PubMed ID: 7909276.
    Abstract:
    Stimulation of quiescent fibroblasts or fibroblast-like cells with growth factors causes a sharp increase in the mRNA levels of several DNA synthesis genes. With most of these genes, the increase in mRNA levels requires at least 2 growth factors [usually platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I)], but the mRNA of the proliferating cell nuclear antigen (PCNA) gene is induced by PDGF only. Since PDGF is known to induce also expression of IGF-I and its receptor, we inquired as to whether the PCNA mRNA induction by PDGF depended on a functional IGF autocrine loop. Using R- cells, i.e., mouse embryo cells in which the IGF-I receptor genes have been disrupted by homologous recombination, we show here that the functional integrity of the IGF-I receptor is obligatory for the PDGF-induced increase in PCNA mRNA levels. However, PCNA pre-mRNA levels are increased by PDGF even in the absence of the IGF-I receptor. These experiments confirm the importance of the IGF-I receptor in the control of cellular proliferation in animal cells, and suggest that one of its functions may be in the processing of certain pre-mRNAs required for orderly cell cycle progression.
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