Regulation of Bovine Bronchial Epithelial Cell Proliferation and Proto-oncogene Expression by Growth Factors

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Abstract
The proto-oncogenes are thought to play important roles in the regulation of cellular growth and differentiation. In order to evaluate the role of proto-oncogenes in the regulation of growth of bronchial epithelial cells, we studied steady-state levels of fos, jun, and myc transcripts in response to fetal calf serum, bovine pituitary extract, and insulin. Extensively quiescent populations of bovine bronchial epithelial cells in growth factor-free medium were stimulated to divide by each of these three additives. We observed rapid but transient increases of fos, jun, and myc expression in association with such growth stimulation. There were no changes in tubulin mRNA levels over the same time periods. Other "growth factors" (epidermal growth factor, hydrocortisone, epinephrine, triiodothyronine, and transferrin) were also studied and did not affect either cell growth or expression of fos, jun, or myc. We further examined the effect of transforming growth factor-beta1 (TGF-beta1) on the above stimulatory effects. TGF-beta1 consistently inhibited the growth induced by fetal calf serum, bovine pituitary extract, or insulin and, interestingly, reduced proto-oncogene myc mRNA level without altering that of fos and jun. In conclusion, proto-oncogenes fos, jun, and myc appear to play a role in the regulation of growth response in bovine bronchial epithelial cells. It is also possible that TGF-beta1 exerts its growth inhibitory effect, at least in part, through the processes that involve the regulation of proto-oncogene myc transcription in these cells.