Insulin and Epidermal Growth Factor's Activation of Extracellular-Signal Regulated Kinases 1/2 and DNA Synthesis is Inhibited by Four Cardiac Hormones

Ying Sun ； Ehrentraud J. Eichelbaum ； Hai Wang ； David L. Vesely

《Journal of Cancer Molecules》 3卷4期 (2007/08) Pp. 113-120

https://doi.org/10.29685/JCM.200708.0003

並列摘要

AIM: This study is to determine if four endogenous growth inhibitors (i.e. four cardiac hormones) can inhibit the activity of extracellular-signal regulated kinases 1/2 (ERK 1/2) stimulated by endogenous growth promoters i.e. insulin and epidermal growth factor (EGF).
METHODS: The phosphorylation of ERK 1/2 was measured with Western blots, while DNA synthesis was measured by bromodeoxyuridine incorporation.
RESULTS: These four peptide hormones, i.e. vessel dilator, kaliuretic peptide, long acting natriuretic peptide, and atrial natriuretic peptide decreased insulin's (10 μM) 66% enhanced phosphorylation in human prostate adenocarcinoma cells to 10%, 8%, 24%, and 13% above non-stimulated ERK 1/2 activity, respectively. The EGF's (50 ng/ml) 66% enhanced phosphorylation of ERK 1/2 in human prostate cancer cells was inhibited to-11% (i.e. 117% decrease), 4%, 13% and 16% by vessel dilator, atrial natriuretic peptide, long acting natriuretic peptide, and kaliuretic peptide compared to nonstimulated ERK 1/2 activity, respectively. In human pancreatic cancer cells insulin and epidermal growth factor stimulated ERK 1/2 to a larger extent, i.e., 98% and 472%, respectively, and this stimulation was decreased to below baseline by the four cardiac hormones. Respective antibodies to these four cardiac hormones blocked their ability to inhibit the ERK 1/2 phosphorylation and DNA synthesis induced by insulin and epidermal growth factor, indicating that their effects are specific.
CONCLUSION: Four endogenous cardiac hormones inhibit EGF and insulin-stimulated ERK 1/2 and DNA synthesis, which may be important for their anti-cancer effects.

並列關鍵字

ERK ； mitogens ； EGF ； Insulin ； natriuretic peptides