A polypeptide growth factor (RDGF) secreted by a human retinoblastoma cell line (Y-79) grown in serum-free defined medium stimulated DNA synthesis up to 36-fold and cellular proliferation by 100% upon 3 days of exposure to quiescent Nakano mouse lens epithelial cells (NKR-11) deprived of serum supplements. The stimulation of DNA synthesis produced by RDGF in the absence of serum could be further potentiated by the presence of 0.1 μg/ml of insulin or 0.1 μg/ml of arginine vasopressin. 12-O-tetradecanoyl-phorbol-13-acetate (TPA), on the other hand, produced a 30-40% decrease in RDGF activity at 1-10 μg/ml of TPA. The stimulation of DNA synthesis produced by RDGF, and its potentiation by the simultaneous addition of insulin, could be sustained after transient exposure (30 min) to RDGF, or RDGF plus insulin, respectively, whereas insulin alone has little effect after exposures of up to 6 h. Nerve growth factor (1.0 pg to 1.0 μg/ml) did not stimulate DNA synthesis or cell division in NKR-11 cells, whereas fibroblast growth factor (FGF) produced an optimal 3-fold stimulation of DNA synthesis at 10 ng/ml. Epidermal growth factor (EGF) activity was optimal and showed a 5-fold increase in DNA synthesis at 100 pg/ml in NKR-11 cells. The early receptor-mediated events that might be responsible for the transition to a proliferative state in quiescent Nakano mouse lens epithelial cells are discussed.
Bibliographical noteFunding Information:
This work was supported by NIH Grants EY-07000, EY-00789 and unrestrictedf unds from the Connecticut Lions Eye Research Foundation, Inc. and Research to Prevent Blindness.