ANTAGONISTIC ACTIONS OF RETINOIC ACID AND DEXAMETHASONE ON ANCHORAGE-INDEPENDENT GROWTH AND EPIDERMAL GROWTH-FACTOR BINDING OF NORMAL RAT-KIDNEY CELLS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (4) , 1635-1641
Abstract
Type .beta. transforming growth factor (TGF-.beta.), in combination with epidermal growth factor (EGF) can induce nonneoplastic normal rat kidney cells to express a transformed phenotype and to form colonies in soft agar. Retinoic acid by itself has no effect on colony formation; but at concentrations of 10-9 M or greater, it can greatly enhance the response of the cells to EGF and TGF-.beta. as measured by colony growth in soft agar and expression of a transformed morphology in monolayer culture. Dexamethasone, at concentrations above 10-9 M, has an opposite effect, inhibiting the TGF-.beta.-dependent formation of colonies in soft agar and restoring a more normal morphology to the cells. Added simultaneously, these 2 modulators act antagonistically; at equimolar concentrations, their opposite effects on colony formation are cancelled. Retinoic acid and dexamethasone also have opposite and antagonistic effects on the binding of 125I-labeled EGF to normal rat kidney cells. Retinoic acid enhances the binding of EGF up to 6-fold, while dexamethasone reduces the binding to 50-60% of control levels. These effects on EGF binding show a dose dependence similar to the effects on colony formation in soft agar and on morphology in monolayer culture. Optimal effects on binding are observed 40-60 h after treatment of the cells. The abilities of retinoic acid and dexamethasone to alter expression of the transformed phenotype induced by treatment of normal rat kidney cells with TGF-.beta. and EGF are mediated at least in part through their effects on the EGF receptor.

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