Epidermal growth factor-stimulated DNA synthesis requires an influx of extracellular calcium

✍ Scribed by Timothy D. Hill; Henrik Kindmark; Alton L. Boynton

• Book ID: 102303151
• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 463 KB
• Volume: 38
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240380208

✦ Synopsis

The dependency of normal cell proliferation on adequate extracellular Ca2 + levels was further investigated by determining the role of Ca2' influx in epidermal growth factor (EGF)-induced rat liver epithelial (T51B) cell DNA synthesis. Fura-2-loaded T51B cells responded with an increase in [Ca2+]i to EGF (5-50 ng/ml) that was blocked by low (25 p M ) extracellular Ca2+ or by pretreatment with 50 pM La3+ to inhibit plasma membrane Ca2' flux. Confluent T51B cells treated for 24 h with EGF (0.1-50 ng/ml) dose-dependently incorporated [3H]-thymidine into cell nuclei. Low extracellular Ca2' or addition of La3f prevented the EGFstimulated rise in labeled nuclei, indicating that a movement of Ca2' into the cell was required for DNA synthesis. This was supported by our findings that bradykinin, which induced a rise in [Ca2+]i by opening plasma membrane Ca2f channels in T51B cells (but not A23187, thrombin or ATP, which raise [Ca2+]i primary through mobilization of intracellular Ca2' stores), potentiated DNA synthesis stimulated by submaximal doses of EGF. Potentiation of the action of EGF by the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA), indicates that activation of protein kinase C and an influx of Ca2+ share a common mechanism for initiating DNA synthesis.