Stimulation by transforming growth factor-beta of epidermal growth factor-dependent growth of aged human fibro-blasts: recovery of high affinity EGE receptors and growth stimulation by EGF.

The stimulatory effects of transforming growth factor beta (TGF-beta) on epidermal growth factor (EGF)-dependent growth of adult and newborn human fibroblasts were investigated. EGF-stimulated growth in low serum of dermal fibroblasts from a 41 year-old adult (HSF-41) was less than half that of newborn foreskin fibroblasts (HFF). The EGF-stimulated growth of HFF after 55 population doublings (HFF-55) was similarly reduced. The decreased growth response to EGF of fibroblasts aged in vivo and in vitro appeared to result principally from a decreased sensitivity to EGF due to a decreased number and affinity of high affinity EGF receptors (H-EGFR). Pre-incubation of HSF-41 and HFF-55 with 25 pM TGF-beta enhanced the growth responses of these cells to EGF and increased the levels of high affinity EGF-binding by these cells. Thus, the stimulation by TGF-beta of EGF-dependent growth of human fibroblasts aged in vivo or in vitro is mediated by increased levels of high affinity EGF binding.