STAT5 contributes to antiapoptosis in melanoma
STAT5 contributes to antiapoptosis in melanoma
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DOI：
10.1097/cmr.0b013e32830ce7d7
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发表时间：
2008-12-01
影响因子：
2.2
通讯作者：
Wellbrock, Claudia
中科院分区：
文献类型：
--
作者：
Hassel, Jessica C.;Winnemoeller, Dirk;Wellbrock, Claudia
恶性黑色素瘤是一种发病率迅速上升的癌症。对原发性肿瘤和肿瘤衍生细胞系的广泛研究揭示，信号转导和转录激活因子（STAT）蛋白，特别是STAT 3和5的不适当激活在各种人类癌症中以高频率发生。我们报道了在剑尾鱼黑色素瘤模型中，STAT 5的组成性激活与黑色素瘤的侵袭性相关。对人黑色素瘤的研究主要集中在STAT 1的功能上，但我们最近发现STAT 5在人黑色素瘤中也被激活。本研究的目的是获得更多关于STAT 5在黑色素瘤中的功能的信息。在这里，我们证明了在小鼠黑素细胞中，STAT 5的激活（通过其酪氨酸磷酸化和易位到细胞核来测量）与其靶基因bcl-X（L）的上调平行。这表明STAT 5在色素细胞中的抗凋亡信号传导中的作用。在人黑色素瘤细胞系中，我们发现STAT 5的组成性激活与bcl-XL的表达相关。人黑色素瘤细胞系A375中显性负性STAT 5的表达导致bcl-XL表达减少和凋亡细胞的急剧增加。与已知抑制干扰素抗增殖作用的STAT 1相反，我们的数据支持STAT 5通过激活抗凋亡蛋白bcl-X（L）在黑色素瘤细胞增殖和存活中的重要作用。请记住，干扰素激活两种STAT蛋白，STAT 5激活可能是黑色素瘤的干扰素抗性的重要性。黑色素瘤研究18：378-385（C）2008年沃尔特斯·克鲁沃健康垂直栏Lippincott威廉姆斯&威尔金斯。
Malignant melanoma is a cancer whose incidence is rising rapidly. Extensive studies of primary tumors and tumor-derived cell lines revealed that inappropriate activation of signal transducer and activator of transcription (STAT) proteins, particularly of STAT3 and 5, occurs with high frequency in various human cancers. We reported that in the Xiphophorus fish melanoma model, constitutive activation of STAT5 correlates with the aggressiveness of melanoma. Investigations in human melanoma mainly focussed on the function of STAT1, but we have shown recently that STAT5 is also activated in human melanoma. The objectives of this investigation were to get more information about the function of STAT5 in melanoma. Here we demonstrate that in murine melanocytes activation of STAT5 measured by its tyrosine phosphorylation and translocation to the nucleus parallels upregulation with its target gene bcl-X(L). This indicates a role for STAT5 in antiapoptotic signaling in pigment cells. In human melanoma cell lines, we found that constitutive activation of STAT5 correlates with expression of bcl-XL. Expression of dominant negative STAT5 in the human melanoma cell line A375 leads to a reduced bcl-XL expression and a dramatic increase of apoptotic cells. In contrast to STAT1, which is known to transduce anti proliferative effects of interferons, our data support a significant role for STAT5 in melanoma cell proliferation and survival via the activation of the antiapoptotic protein bcl-X(L). Keeping in mind that interferons activate both STAT proteins, STAT5 activation could be of importance in interferon resistance of melanoma. Melanoma Res 18:378-385 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.