Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma.
Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma.
复制标题
DOI：
10.1038/bjc.2011.249
复制
发表时间：
2011-08-09
影响因子：
8.8
通讯作者：
Gallagher, W. M.
中科院分区：
文献类型：
--
作者：
Gremel, G.;Ryan, D.;Rafferty, M.;Lanigan, F.;Hegarty, S.;Lavelle, M.;Murphy, I.;Unwin, L.;Joyce, C.;Faller, W.;McDermott, E. W.;Sheahan, K.;Ponten, F.;Gallagher, W. M.
含有同源框的转录因子MSX 2是胚胎发育的关键调节因子，并被认为在乳腺癌和胰腺癌中起作用。使用选择的二维和三维体外测定和组织微阵列（TMA），MSX 2在恶性黑色素瘤中的临床和功能相关性进行了探索。应用强力霉素诱导的过表达系统在体外研究MSX 2的相关性。对于TMA构建，使用来自218名黑素瘤患者的肿瘤材料。MSX 2的异位表达诱导了细胞凋亡，降低了三维培养中黑色素瘤细胞的侵袭能力。MSX 2过表达显示影响与细胞侵袭和存活相关的几种信号通路。观察到N-Cadherin的下调、p21的诱导以及BCL 2和Survivin的抑制。发现细胞质MSX 2表达与增加的无复发生存率显著相关（P=0.008）。MSX 2的核表达没有导致显著的存活相关性，这表明MSX 2的有益作用可能不依赖于其DNA结合活性。MSX 2可能是黑色素瘤细胞侵袭和存活的重要调节因子。该蛋白质的胞浆表达被鉴定为恶性黑素瘤患者预后良好的生物标志物。
The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer. Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used. Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity. MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.
登录
查看更多内容
影响因子：
4.7
作者：
Gallagher, WM;Bergin, OE;Easty, DJ
通讯作者：
Easty, DJ
影响因子：
64.5
作者：
JABS, EW;MULLER, U;MAXSON, R
通讯作者：
MAXSON, R
影响因子：
1.8
作者：
Chen, D;Zhao, M;Mundy, GR
通讯作者：
Mundy, GR
影响因子：
2.7
作者：
Lallemand, Yvan;Bensoussan, Vardina;Robert, Benoit
通讯作者：
Robert, Benoit
影响因子：
6
作者：
Satoh, Kennichi;Hamada, Shin;Shimosegawa, Tooru
通讯作者：
Shimosegawa, Tooru