UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Br J Cancer. 2011 Aug 9;105(4):565-74. doi: 10.1038/bjc.2011.249. Epub 2011 Jul 5.
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.
含有转录因子 MSX2 的同源盒是胚胎发育的关键调节剂，并且已经被牵连到乳腺癌和胰腺癌中。
使用一系列二维和三维体外测定法和组织微阵列（TMA），探索 MSX2 在恶性黑色素瘤中的临床和功能相关性。应用强力霉素诱导的过表达系统来研究 MSX2 在体外的相关性。为了构建 TMA，使用了 218 例黑色素瘤患者的肿瘤材料。
MSX2 的异位表达导致凋亡的诱导，并降低了黑色素瘤细胞在三维培养中的侵袭能力。MSX2 的过表达被证明会影响与细胞侵袭和存活相关的几种信号通路。观察到 N-钙粘蛋白的下调、p21 的诱导以及 BCL2 和 Survivin 的抑制。细胞质 MSX2 表达与无复发生存率的显著增加相关（P=0.008）。MSX2 的核表达并未导致显著的生存相关性，这表明 MSX2 的有益作用可能与其 DNA 结合活性无关。
MSX2 可能是黑色素瘤细胞侵袭和存活的重要调节剂。该蛋白的细胞质表达被鉴定为恶性黑色素瘤患者预后良好的生物标志物。
