STUDIES OF ONCOGENE EXPRESSION DURING CELLULAR GROWTH AND DIFFERENTIATION

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Proto-oncogene expression was studied in the BALB-MK epithelial cell line following mitogenic stimulation with epidermal growth factor (EGF). The following results were obtained: C-fos expression: C-fos is undetectable in total cellular RNA of quiescent cells prior to addition of EGF. After addition of EGF, c-fos expression rises sharply to a sharp peak, one hour post-stimulation. It then drops off rapidly to low but detectable levels within the next few hours. C-myc expression: These cells express constitutively high levels of c-myc when quiescent. When EGF is added, c-myc expression rises four- to eight-fold to a plateau beginning at two hours and ending at eight hours post-stimulation. It then steadily declines to steady-state levels higher than prior to addition of EGF. Effects of TPA: The tumor promoter TPA was found to mimic the mitogenic effects of EGF and, like EGF, to stimulate a sharp one-hour peak of c-fos when given to BALB-MK cells in the absence of EGF. Ca++ and c-fos expression: Ca++, which is a signal for terminal differentiation in BALB-MK cells, was found to cause a decline in c-fos expression.