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Epidermal growth factor's activation of Ras is inhibited by four cardiac hormones

Ying Sun1, Ehrentraud J Eichelbaum, Anne Lenz

  • 1University of South Florida Cardiac Hormone Center and James A. Haley Veterans Medical Center, Tampa, FL 33612, USA.

European Journal of Clinical Investigation
|April 1, 2010
PubMed
Abstract

Insights

Four cardiac hormones, including atrial natriuretic peptide, show anticancer effects by inhibiting epidermal growth factor (EGF) activation of Ras. This suggests a novel therapeutic strategy for cancer treatment.

Area of Science:

  • Cardiovascular Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Four cardiac hormones, atrial natriuretic peptide (ANP), vessel dilator (VD), kaliuretic peptide (KP), and long-acting natriuretic peptide (LANP), are synthesized from the same gene and exhibit anticancer properties.
  • Epidermal growth factor (EGF) plays a role in cancer development through the activation of the Ras signaling pathway.

Purpose of the Study:

  • To investigate the potential of four cardiac hormones to inhibit mitogen-induced activation of Ras.
  • To explore the anticancer mechanisms of cardiac hormones involving the Ras pathway.

Main Methods:

  • Assessing the ability of ANP, VD, KP, and LANP to inhibit EGF-stimulated Ras activation in vitro.
  • Utilizing specific antibodies to confirm the specificity of cardiac hormone inhibition of Ras activation.

Main Results:

  • EGF significantly increased Ras activation in a dose-dependent manner.
  • VD, LANP, ANP, and KP inhibited EGF-induced Ras activation by 73%, 79%, 33%, and 45%, respectively, at 1 μM concentrations.
  • Specific antibodies blocked the inhibitory effects of cardiac hormones on Ras activation, confirming specificity.

Conclusions:

  • The four cardiac hormones specifically inhibit EGF-induced activation of Ras.
  • These findings suggest that the anticancer effects of cardiac hormones may involve the inhibition of Ras activation stimulated by mitogens like EGF, as well as basal Ras activity.

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