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Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways
Departments of Internal Medicine, Molecular Pharmacology and Physiology, Cardiac Hormone Center, University of South Florida Health Sciences Center, J. A. Haley Veterans Medical Center-151, 13000 Bruce B. Downs Blvd., Tampa, Florida 33612, USA
Received: 18 February 2011; in revised form: 2 March 2011 / Accepted: 3 March 2011 / Published: 8 March 2011
Abstract: The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide prohormone which contains four peptide hormones, i.e., atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian carcinomas as well as small-cell and squamous cell lung cancer cells in cell culture. In vivo, these four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, two-thirds of human breast cancers, and up to 86% of human small-cell lung cancers growing in athymic mice. Their signaling in cancer cells includes inhibition of up to 95% of the basal activity of Ras, 98% inhibition of the phosphorylation of the MEK 1/2 kinases and 97% inhibition of the activation of basal activity of the ERK 1/2 kinases mediated via the intracellular messenger cyclic GMP. They also completely block the activity of mitogens such as epidermal growth factor’s ability to stimulate ERK and Ras. They do not inhibit the activity of ERK in healthy cells such as human fibroblasts. The final step in their anticancer mechanism of action is that they enter the nucleus as demonstrated by immunocytochemical studies to inhibit DNA synthesis within cancer cells.
Keywords: Ras; MEK 1/2 kinases; ERK 1/2 kinases; DNA synthesis; cancer; signaling
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Vesely, D.L. Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways. Cancers 2011, 3, 1182-1194.
Vesely DL. Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways. Cancers. 2011; 3(1):1182-1194.
Vesely, David L. 2011. "Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways." Cancers 3, no. 1: 1182-1194.