Epidermal growth factor initiates DNA synthesis after a time-dependent sequence of regulatory events in Swiss 3T3 cells—interactions with hormones and growth factors

✍ Scribed by Angela M. Otto; Marie-Odile Ulrich; Luis Jimenez de Asua

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: English
• Weight: 701 KB
• Volume: 108
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041080205

✦ Synopsis

Epidermal growth factor (EGF) stimulates the initiation of DNA synthesis in Swiss 3T3 cells after a constant prereplicative period of 14-15 hours. The final rate of initiation follows apparent first-order kinetics and can thus be quantified by a rate constant k. The value of k can be changed by later additions during the prereplicative period: When cells stimulated by a very low concentration of EGF, alone or with insulin, which results in a relatively low value of k, receive a saturating amount of EGF at 15 hours, then k is markedly increased after 4-6 hours. Insulin alone (up to 200 ng/ml) is unable to set the lag phase, but does have a synergistic effect on the value of k given by EGF. When added at 15 hours, insulin also increases k, but after a delay of 4-6 hours. In contrast, both hydrocortisone and prostaglandin E, (PGE,) inhibit the stimulation of DNA synthesis by EGF only during the first 8 hours of the prereplicative period of decreasing the value of k.

Prostaglandin FzI, (PGF,,), which stimulates DNA synthesis in a similar mode as EGF, when added with EGF has a synergistic effect on DNA synthesis. This suggests that EGF and PGF,,, nevertheless, act through different regulatory events.