Department of Medicine, James A. Haley VA Medical Center, Tampa, FL, USA.
Eur J Clin Invest. 2013 Nov;43(11):1156-62. doi: 10.1111/eci.12153. Epub 2013 Sep 2.
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.
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.
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.
Four cardiac hormones are potent inhibitors of c-Fos and c-Jun proto-oncogenes within the nucleus of cancer cells.
c-Fos 是一种细胞原癌基因，它与 c-Jun 原癌基因二聚化形成 AP-1 转录因子，上调参与增殖和癌症形成的基因转录。四种心脏激素，即长效利钠肽（LANP）、血管扩张剂、利钾肽（KP）和心房利钠肽（ANP），在体内具有抗癌作用，是 Ras-MEK 1/2-ERK 1/2 激酶级联和信号转导和转录激活因子-3（STAT-3）的有效抑制剂，可激活 c-Fos 和 c-Jun。研究了这四种心脏激素对癌细胞核中原癌基因 c-Fos 和 c-Jun 的影响。
评估了四种心脏激素降低三种人癌细胞系提取核中原癌基因 c-Fos 和 c-Jun 的能力，通过 ELISA 进行测量。
血管扩张剂、LANP、KP 和 ANP 在 100 pM-10 μM 的浓度范围内，最大程度地将人肝癌细胞中的 c-Fos 降低了 61%、60%、61%和 59%，小细胞肺癌细胞中的 c-Fos 降低了 82%、74%、78%和 74%，人肾腺癌中的 c-Fos 降低了 82%、73%、78%和 74%。血管扩张剂、LANP、KP 和 ANP 最大程度地将人肝癌细胞中的 c-Jun 降低了 43%、31%、61%和 35%，小细胞肺癌细胞中的 c-Jun 降低了 65%、49%、59%和 40%，肾癌细胞中的 c-Jun 降低了 47%、43%、57%和 49%。
四种心脏激素是癌细胞核中 c-Fos 和 c-Jun 原癌基因的有效抑制剂。
