IDENTIFICATION OF ENDOTHELIN-1 IN THE PATHOPHYSIOLOGY OF METASTATIC ADENOCARCINOMA OF THE PROSTATE
IDENTIFICATION OF ENDOTHELIN-1 IN THE PATHOPHYSIOLOGY OF METASTATIC ADENOCARCINOMA OF THE PROSTATE
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DOI：
10.1038/nm0995-944
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发表时间：
1995-09-01
期刊：
影响因子：
82.9
通讯作者：
SIMONS, JW
中科院分区：
文献类型：
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作者：
NELSON, JB;HEDICAN, SP;SIMONS, JW
前列腺癌是美国男性癌症死亡的第二大常见原因，晚期激素难治性疾病的特点是痛苦的成骨细胞骨转移。内皮素-1，通常被认为是一种有效的血管收缩因子，是一种正常的射精蛋白，也能刺激成骨细胞。我们在这里显示，在转移性前列腺癌患者中，血浆免疫反应性内皮素浓度显著升高，并且每个被测试的人前列腺癌细胞系都产生内皮素-1信使RNA并分泌免疫反应性内皮素。外源性ET-1在体外是前列腺癌有丝分裂原，促进新骨形成过程中碱性磷酸酶的活性，提示异位ET-1可能是转移性前列腺癌成骨反应的介导物。
Prostate cancer is the second most common cause of death from cancer in U.S. men, and advanced, hormone-refractory disease is characterized by painful osteoblastic bone metastases. Endothelin-1, more commonly known as a potent vasoconstrictor, is a normal ejaculate protein that also stimulates osteoblasts. We show here that plasma immunoreactive endothelin concentrations are significantly elevated in men with metastatic prostate cancer and that every human prostate cancer cell line tested produces endothelin-1 messenger RNA and secretes immunoreactive endothelin. Exogenous endothelin-1 is a prostate cancer mitogen in vitro and increases alkaline phosphatase activity in new bone formation, indicating that ectopic endothelin-1 may be a mediator of the osteoblastic response of bone to metastatic prostate cancer.