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Synergistic effects of endothelin-1 (ET-1) and transforming growth factor alpha (TGF-α) or epidermal growth factor (EGF) on DNA replication and G1 to S phase transition

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Abstract

The cooperative cell kinetic actions of ET-1 with TGF-α or EGF in normal rat kidney fibroblasts (NRK-49F) and KNRK cells (Kirsten MSV transformed) were analyzed by [3H]-thymidine incorporation assay and flow cytometry. A marked synergistic effect of TGF-α and ET-1 (or EGF and ET-1) on DNA synthesis and G1 to S transition was observed in NRK cells; 15–20% S for TGF-α and 12% S for ET-1 alone but 45–50% S in combination. There was no detectable effect on cell cycle kinetics by TGF-α (1 ng/ml) or EGF (1 ng/ml) plus ET-1 (1 ng/ml) in KNRK cells treated for 22 hours. Insulin, insulin-like growth factor I (IGF-I), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), and transforming growth factor β (TGF-β) were also tested and found to have no significant synergistic effects on ET-1 actions. Our findings suggest that the combination of TGF-α (EGF) and ET-1 is an important part of an intricate network which coordinates progression of G1 to S phase in normal cells.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, 72205, Little Rock, AR

    Yun-Chi Yeh & Hsing-Wu Yeh

  2. Department of Anatomy, College of Medicine, University of Arkansas for Medical Sciences, 72205, Little Rock, AR

    E. Robert Burns

  3. Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 02115, Boston, MA

    John Yeh

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  1. Yun-Chi Yeh
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  2. E. Robert Burns
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  3. John Yeh
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  4. Hsing-Wu Yeh
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Yeh, YC., Burns, E.R., Yeh, J. et al. Synergistic effects of endothelin-1 (ET-1) and transforming growth factor alpha (TGF-α) or epidermal growth factor (EGF) on DNA replication and G1 to S phase transition. Biosci Rep 11, 171–180 (1991). https://doi.org/10.1007/BF01182486

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  • DOI: https://doi.org/10.1007/BF01182486

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