Immunocytochemical localization of atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide, and kaliuretic peptide in human pancreatic adenocarcinomas.
We recently found that four peptide hormones synthesized by the same gene completely inhibit the growth of human pancreatic adenocarcinomas in athymic mice. The present immunocytochemical investigation was designed to determine where in the adenocarcinomas these peptide hormones localize. Atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide, and kaliuretic peptide localized to the cytoplasm and nucleus of the human pancreatic adenocarcinomas, which is consistent with their ability to decrease DNA synthesis in the nucleus of this cancer. In this first investigation of where these peptide hormones with anticancer effects localize in any cancer, these peptide hormones also localized to the endothelium of capillaries and fibroblasts within these cancers. This is the first demonstration of growth-inhibiting peptide hormones localizing to the nucleus, where they inhibit DNA synthesis and may interact with growth-promoting hormones that localize there as the etiology of their ability to inhibit the growth of adenocarcinomas both in vitro and in vivo.
Saba
Sabiha R
SR
Department of Biochemistry and Molecular Biology, University of South Florida Cardiac Hormone Center, Tampa 33612, Florida, USA.
Garces
Amanda H
AH
Clark
Linda C
LC
Soto
John
J
Gower
William R
WR
Vesely
David L
DL
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*
D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054547:atrial natriuretic factor prohormone (1-30), human; D009320:Atrial Natriuretic Factor