期刊
SCIENCE
卷 331, 期 6018, 页码 768-772出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1198785
关键词
-
资金
- National Institutes of Health (NIH) [DK54983]
- Yale Center for Human Genetics and Genomics
- Yale NIH O'Brien Center for Kidney Research
- Yale NIH
- Swedish Cancer Society
- Swedish Research Council
- Lions Cancer Fund, Uppsala
- Fondation Leducq Transatlantic Network in Hypertension
Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in and near the selectivity filter of the potassium (K+) channel KCNJ5 that are present in 8 of 22 human APAs studied. Both produce increased sodium (Na+) conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium (Ca2+) entry, the signal for aldosterone production and cell proliferation. Similarly, we identify an inherited KCNJ5 mutation that produces increased Na+ conductance in a Mendelian form of severe aldosteronism and massive bilateral adrenal hyperplasia. These findings explain pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive cell proliferation and hormone production.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据