Cardiac hormones target nuclear oncogenes c‐Fos and c‐Jun in carcinoma cells. (2nd September 2013)

• Record Type: Journal Article
• Authors: Manimala, Neil J.; Frost, Chelsea D.; Lane, Meghan L.; Higuera, Mariana; Beg, Rana; Vesely, David L.
• Is Part Of: European journal of clinical investigation. Volume 43:Number 11(2013:Nov.)
• Page Start: 1156
• Page End: 1162
• Publication Date: 2013-09-02
• Subjects: Pathology -- Periodicals; Medical research -- Periodicals; 616.075
• DOI: 10.1111/eci.12153
• Languages: English
• ISSNs: 0014-2972

Abstract

<abstract abstract-type="main" id="eci12153-abs-0001"> <title>Abstract</title> <sec id="eci12153-sec-0001" sec-type="section"> <title>Background</title> <p>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 <italic>in vivo</italic> 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.</p> </sec> <sec id="eci12153-sec-0002" sec-type="section"> <title>Materials and methods</title> <p>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.</p> </sec> <sec id="eci12153-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="eci12153-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Four cardiac hormones are potent inhibitors of c‐Fos and c‐Jun proto‐oncogenes within the nucleus of cancer cells.</p> </sec> </abstract>