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Cardiac hormones target nuclear oncogenes c‐ F os and c‐ J un in carcinoma cells
Author(s) -
Manimala Neil J.,
Frost Chelsea D.,
Lane Meghan L.,
Higuera Mariana,
Beg Rana,
Vesely David L.
Publication year - 2013
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12153
Subject(s) - cancer cell , cancer research , endocrinology , stat3 , oncogene , medicine , atrial natriuretic peptide , transcription factor , biology , hormone , dilator , cancer , chemistry , signal transduction , microbiology and biotechnology , cell cycle , gene , biochemistry
Background c‐ F os is a cellular proto‐oncogene which dimerizes with c‐ J un 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 R as‐ MEK 1/2‐ ERK 1/2 kinase cascade and signal transducer and activator of transcription‐3 ( STAT ‐3) that activate c‐ F os and c‐ J un. These four cardiac hormones were investigated for their effects on proto‐oncogenes c‐ F os and c‐ J un within the nucleus of cancer cells. Materials and methods Four cardiac hormones were evaluated for their ability to decrease proto‐oncogenes c‐ F os and c‐ J un, 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‐ F os 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‐ J un 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. Conclusion Four cardiac hormones are potent inhibitors of c‐ F os and c‐ J un proto‐oncogenes within the nucleus of cancer cells.