CARDIAC MYOCYTE HYPERTROPHY IS ASSOCIATED WITH C-MYC PROTOONCOGENE EXPRESSION
CARDIAC MYOCYTE HYPERTROPHY IS ASSOCIATED WITH C-MYC PROTOONCOGENE EXPRESSION
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DOI：
10.1073/pnas.83.21.8348
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发表时间：
1986-11-01
影响因子：
11.1
通讯作者：
WILLIAMS, LT
中科院分区：
文献类型：
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作者：
STARKSEN, NF;SIMPSON, PC;WILLIAMS, LT
睾丸诱导细胞肥大的机制尚不清楚。用α 1-肾上腺素能试剂、佛波醇酯和血清刺激心肌细胞可诱导原代培养物中非分裂心肌细胞的细胞大小增加。在该细胞肥大模型中研究了已知在生长因子诱导的细胞分裂中增加的c-myc基因的表达。α-肾上腺素能激动剂去甲肾上腺素（0.002-20 μ M）使c-myc编码的mRNA水平增加到对照水平的10倍。这种增加在30分钟时可检测到，在2小时时达到峰值，并在刺激后6小时恢复到基线。去甲肾上腺素反应被α 1-拮抗剂特拉唑嗪（2 μ M）消除，但不受β-肾上腺素能拮抗剂普萘洛尔（2 μ M），并且仅被α 2-肾上腺素能拮抗剂育亨宾（2 μ M）轻微减弱（25%）。血清和佛波酯肿瘤促进剂佛波酯12-肉豆蔻酸酯13-乙酸酯也增强了心肌细胞培养物中c-myc的表达。这些发现表明，心肌细胞肥大的诱导与c-myc基因的表达增强有关，并表明，经尿道诱导的细胞肥大和细胞分裂共享共同的机制途径。
The mechanism of hormonally induced cell hypertrophy is unknown. Stimulation of cardiac myocytes by .alpha.1-adrenergic agents, phorbol esters, and serum induces an increase in the cell size of nondividing cardiac myocytes in primary culture. Expression of the c-myc gene, known to be increased in growth factor-induced cell division, was studied in this model of cell hypertrophy. The .alpha.-adrenergic agonist norepinephrine (0.002-20 .mu.M) increased levels of c-myc-encoded mRNA to 10-fold over control levels. This increase was detectable at 30 min, peaked at 2 hr, and returned to baseline by 6 hr after stimulation. The norepinephrine response was abolished by the .alpha.1-antagonist terazosin (2 .mu.M) but was not affected by the .beta.-adrenergic antagonist propranolol (2 .mu.M) and was only slightly (25%) attenuated by the .alpha.2-adrenergic antagonist yohimbine (2 .mu.M). Serum and the phorbol ester tumor promoter phorbol 12-myristate 13-acetate also enhanced c-myc expression in cardiac myocyte cultures. These findings show that the induction of cardiac myocyte hypertrophy is associated with enhanced expression of the c-myc gene and suggest that hormonally induced cell hypertrophy and cell division share common mechanistic pathways.