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Action of Epidermal Growth Factor and Retinoids on Anchorage-dependent and -independent Growth of Nontransformed Rat Kidney Cells

Laboratories of Cellular Carcinogenesis and Tumor Promotion [A. M. J.] and Immunodiagnosis [R. H. G.], National Cancer Institute, Bethesda, Maryland 20205

Treatment of two nontransformed rat kidney cell lines with either retinoic acid or epidermal growth factor enhances anchorage-dependent cell growth and reduces cell substratum adhesiveness significantly, whereas the cell morphology is only moderately affected. Simultaneous treatment of these cells with these factors results in a dramatic change in cell morphology and increases cell growth and reduces cell substratum adhesiveness even further.

Treatment of nontransformed rat kidney cells with certain retinoids enhances the binding of ¹²⁵I-labeled mouse epidermal growth factor 2- to 3-fold. Addition of epidermal growth factor stimulates anchorage-independent growth of these cells. Retinoids enhance colony-forming ability in soft agar produced by epidermal growth factor, although retinoids by themselves do not affect anchorage-independent growth. Growth in soft agar induced by epidermal growth factor or epidermal growth factor plus retinoic acid treatments appears to be a reversible trait. Addition of epidermal growth factor stimulates secretion of plasminogen activator, whereas this production is not influenced by retinoids. A transformed rat kidney cell line, which exhibits very low epidermal growth factor binding and grows progressively in soft agar, is not significantly affected by retinoid treatment.

¹ To whom correspondence should be addressed, at National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, N.C. 27709.

² Present address: Cancer Metastasis Research Group, Department of Immunology and Infectious Disease, Pfizer Central Research, Pfizer, Inc., Groton, Conn. 06340.

Received 8/23/82. Accepted 1/14/83.