title: Cardiac hormones target nuclear oncogenes c-Fos and c-Jun in carcinoma cells.
abstract: BACKGROUND
  c-Fos is a cellular proto-oncogene which dimerizes with c-Jun proto-oncogene to form AP-1 transcription factor, which upregulates transcription of genes involved in proliferation and cancer formation. Four cardiac hormones, that is, long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide (KP) and atrial natriuretic peptide (ANP) with anticancer effects in vivo are potent inhibitors of the Ras-MEK 1/2-ERK 1/2 kinase cascade and signal transducer and activator of transcription-3 (STAT-3) that activate c-Fos and c-Jun. These four cardiac hormones were investigated for their effects on proto-oncogenes c-Fos and c-Jun within the nucleus of cancer cells.
  
  
  METHODS
  Four cardiac hormones were evaluated for their ability to decrease proto-oncogenes c-Fos and c-Jun, measured by ELISA in extracted nuclei of three human cancer cell lines.
  
  
  RESULTS
  Vessel dilator, LANP, KP and ANP over a concentration range of 100 pM-10 μM, maximally decreased c-Fos by 61%, 60%, 61% and 59% in human hepatocellular cancer cells, by 82%, 74%, 78% and 74% in small-cell lung cancer cells, and by 82%, 73%, 78% and 74% in human renal adenocarcinoma cells. c-Jun was maximally reduced by vessel dilator, LANP, KP and ANP by 43%, 31%, 61% and 35% in hepatocellular cancer cells, by 65%, 49%, 59% and 40% in small-cell lung cancer cells, and by 47%, 43%, 57% and 49% in renal cancer cells.
  
  
  CONCLUSIONS
  Four cardiac hormones are potent inhibitors of c-Fos and c-Jun proto-oncogenes within the nucleus of cancer cells.
authors.affiliation: Department of Medicine, James A. Haley VA Medical Center, Tampa, FL, USA.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Manimala
authors.forename: Chelsea D
authors.initials: CD
authors.lastname: Frost
authors.forename: Meghan L
authors.initials: ML
authors.lastname: Lane
authors.forename: Mariana
authors.initials: M
authors.lastname: Higuera
authors.forename: Rana
authors.initials: R
authors.lastname: Beg
authors.forename: David L
authors.initials: DL
authors.lastname: Vesely
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; C000715470:MAS1 protein, human; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D011498:Protein Precursors; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C075322:atrial natriuretic factor precursor (79-98); C054547:atrial natriuretic factor prohormone (1-30), human; C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor
keywords: Atrial natriuretic peptide; c-Fos; c-Jun; kaliuretic peptide; long-acting natriuretic peptide; vessel dilator