Epidermal growth factor's activation of Ras is inhibited by four cardiac hormones.
BACKGROUND
Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, have anticancer effects in vitro and in vivo. Epidermal growth factor's mechanism of cancer formation involves the activation of Ras.


METHODS
These four cardiac hormones were evaluated for their ability to inhibit mitogen (epidermal growth factor) activation of Ras.


RESULTS
Epidermal growth factor increased the activation of Ras by 68%, 85% and 90% at its 1, 2 and 5 ng mL(-1) concentrations. Vessel dilator, long-acting natriuretic peptide, atrial natriuretic peptide and kaliuretic peptide inhibited 5 ng mL(-1) epidermal growth factor's stimulation of Ras by 73%, 79%, 33% and 45%, respectively, at their 1 microM concentrations. Their effects on epidermal growth factor's activation of Ras were specific with addition of the cardiac hormones' respective antibodies (5 microM) blocking 95%, 93%, 100% and 100% (P < 0.001 for each) of their ability to inhibit epidermal growth factor's stimulation of Ras.


CONCLUSIONS
Four cardiac hormones specifically inhibit epidermal growth factor's activation of Ras. This investigation would suggest that these cardiac hormones' anticancer effects involve the inhibition of mitogens such as epidermal growth factor's ability to activate Ras as well as inhibiting unstimulated basal activity of Ras.
Sun
Ying
Y
University of South Florida Cardiac Hormone Center and James A. Haley Veterans Medical Center, Tampa, FL 33612, USA.
Eichelbaum
Ehrentraud J
EJ
Lenz
Anne
A
Wang
Hai
H
Vesely
David L
DL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism*; D011905:Genes, ras; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor; D009320:Atrial Natriuretic Factor