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首页> 外文期刊>American Journal of Physiology >Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways.
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Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways.

机译：雌二醇和他莫昔芬刺激LAM相关血管平滑肌脂肪瘤细胞的生长，并激活基因组和非基因组信号通路。

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Lymphangioleiomyomatosis (LAM) is a progressive lung disease affecting almost exclusively women. The reasons for this strong gender predisposition are poorly understood. Renal angiomyolipomas occur in 50-60% of sporadic LAM patients. The smooth muscle cells of pulmonary LAM and renal angiomyolipomas are nearly indistinguishable morphologically. Here, we report the first successful cell culture of a LAM-associated renal angiomyolipoma. The cells carried inactivating mutations in both alleles of the TSC2 gene and expressed estrogen receptor , estrogen receptor , and androgen receptor. To elucidate the cellular pathways through which steroid hormones influence LAM pathogenesis, we treated the cells with both estradiol and tamoxifen. Cell growth was stimulated by estradiol, associated with phosphorylation of p44/42 MAPK at 5 min and an increase in c-myc expression at 4 h. Tamoxifen citrate also stimulated cell growth, associated with increased phosphorylation of p44/42 MAPK and expression of c-myc, indicating that tamoxifen has agonist effects on angiomyolipoma cells. This response to tamoxifen in human angiomyolipoma cells differs from prior studies of Eker rat leiomyoma cells, possibly reflecting cell type or species differences in cells lacking tuberin. Our data provide the first evidence that estradiol stimulates the growth of angiomyolipoma cells, that tamoxifen has agonist effects in angiomyolipoma cells, and that estradiol and tamoxifen impact both genomic and nongenomic signaling pathways in angiomyolipoma cells. The responsiveness of angiomyolipoma cells to estradiol may be related to the underlying reasons that LAM affects primarily women.
机译：淋巴管平滑肌肌瘤病（LAM）是一种进行性肺部疾病，几乎仅影响女性。人们对这种性别倾向很强的原因了解甚少。肾血管肌脂瘤发生在50-60％的散发性LAM患者中。肺LAM和肾血管平滑肌脂肪瘤的平滑肌细胞在形态学上几乎无法区分。在这里，我们报告了首次成功的LAM相关肾血管平滑肌脂肪细胞培养。这些细胞在TSC2基因的两个等位基因中均具有失活突变，并表达雌激素受体，雌激素受体和雄激素受体。为了阐明类固醇激素影响LAM发病机理的细胞途径，我们用雌二醇和他莫昔芬对细胞进行了处理。雌二醇刺激细胞生长，与5分钟时p44 / 42 MAPK磷酸化和4小时c-myc表达增加有关。柠檬酸他莫昔芬还刺激细胞生长，与p44 / 42 MAPK磷酸化增加和c-myc表达有关，表明他莫昔芬对血管平滑肌脂肪瘤细胞具有激动作用。对人血管平滑肌脂肪瘤细胞中他莫昔芬的这种反应与先前对Eker大鼠平滑肌瘤细胞的研究不同，可能反映了缺乏结核菌素的细胞的细胞类型或物种差异。我们的数据提供了第一个证据，证明雌二醇刺激血管平滑肌脂肪瘤细胞的生长，他莫昔芬对血管平滑肌脂肪瘤细胞具有激动作用，并且雌二醇和他莫昔芬影响血管平滑肌脂肪瘤细胞的基因组和非基因组信号通路。血管平滑肌脂肪细胞对雌二醇的反应性可能与LAM主要影响女性的潜在原因有关。

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