Dickkopf-1 activates cell death in MDA-MB435 melanoma cells
Dickkopf-1 activates cell death in MDA-MB435 melanoma cells
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DOI：
10.1016/j.bbrc.2006.11.079
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发表时间：
2007-01-19
影响因子：
3.1
通讯作者：
Zarbl, Helmut
中科院分区：
文献类型：
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作者：
Mikheev, Andrei M.;Mikheeva, Svetlana A.;Zarbl, Helmut
Dickkopf-I (DKK-1) 是已知的经典 Wnt 通路抑制剂。最近的研究强烈表明 DKK-1 表达的激活可抑制细胞致瘤性。最近发现黑色素瘤中 DKK-1 水平降低。然而，尚不清楚黑色素瘤细胞中 DKK-1 的激活是否会抑制细胞致瘤性。在本研究中，我们在黑色素瘤细胞系 MDA-MB435 中过表达 DKK-1。我们发现，虽然 DKK-1 不影响软琼脂中的细胞生长，但在裸鼠体内观察到微弱但显着的致瘤性抑制。对所得肿瘤的分析揭示了细胞死亡的激活。在源自用 DKK-1 转导的细胞的肿瘤中，肿瘤块中充满了坏死区域。在源自对照细胞的肿瘤中，坏死区域仅限于中心区域，这是裸鼠中生长的大肿瘤的共同特征。 TUNEL 测定显示，在源自用 DKK-1 转导的细胞的肿瘤中，沿着肿瘤坏死和存活区域的边界检测到凋亡细胞，表明凋亡过程显着增加。因此，我们的结果表明，黑色素瘤细胞中 DKK-1 的激活导致体内细胞凋亡的激活，因此与裸鼠中的肿瘤生长不相容。 (c) 2006 Elsevier Inc. 保留所有权利。
Dickkopf-I (DKK-1) is known inhibitor of the canonical Wnt pathway. Recent studies strongly suggested that activation of DKK-1 expression results in inhibition of cell tumorigenicity. Reduced levels of DKK-1 in melanomas were recently shown. However, it is not known if DKK-1 activation in melanoma cells will inhibit cell tumorigenicity. In the present study, we overexpressed DKK-1 in melanoma cell line MDA-MB435. We show that while DKK-1 did not affect cell growth in soft agar, weak but significant inhibition of tumorigenicity in nude mice in vivo was observed. Analysis of resulting tumors revealed activation of cell death. In tumors originating from cells transduced with DKK-1, tumor mass was permeated with areas of necrosis. In tumors, originated from control cells, areas of necrosis were limited to the central region, a common feature of large tumors growing in nude mice. TUNEL assay revealed that in tumors originating from cells transduced with DKK-1 apoptotic cells were detected along the border of necrotic and viable areas of the tumors indicating significant increase in apoptotic process. Thus, our results indicate that activation of DKK-1 in melanoma cells leads to activation of apoptosis in vivo and, thus, is incompatible with tumor growth in nude mice. (c) 2006 Elsevier Inc. All rights reserved.