University College Dublin School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Breast Cancer Res. 2010;12(4):R59. doi: 10.1186/bcr2621. Epub 2010 Aug 3.
The homeobox-containing transcription factor muscle segment homeobox 2 (Msx2) plays an important role in mammary gland development. However, the clinical implications of Msx2 expression in breast cancer are unclear. The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro.
Msx2 gene expression was first examined in a well-validated breast cancer transcriptomic dataset of 295 patients. Msx2 protein expression was then evaluated by immunohistochemistry in a tissue microarray (TMA) containing 281 invasive breast tumours. Finally, to assess the functional role of Msx2 in vitro, Msx2 was ectopically expressed in a highly invasive breast tumour cell line (MDA-MB-231) and an immortalised breast cell line (MCF10a), and these cell lines were examined for changes in growth rate, cell death and cell signalling.
Examination of Msx2 mRNA expression in a breast cancer transcriptomic dataset demonstrated that increased levels of Msx2 were associated with good prognosis (P = 0.011). Evaluation of Msx2 protein expression on a TMA revealed that Msx2 was detectable in both tumour cell nuclei and cytoplasm. Cytoplasmic Msx2 expression was associated with low grade tumours (P = 0.012) and Ki67 negativity (P = 0.018). Nuclear Msx2 correlated with low-grade tumours (P = 0.015), estrogen receptor positivity (P = 0.038), low Ki67 (P = 0.005) and high cyclin D1 expression (P = 0.037). Increased cytoplasmic Msx2 expression was associated with a prolonged breast cancer-specific survival (P = 0.049), recurrence-free survival (P = 0.029) and overall survival (P = 0.019). Ectopic expression of Msx2 in breast cell lines resulted in radically decreased cell viability mediated by induction of cell death via apoptosis. Further analysis of Msx2-expressing cells revealed increased levels of p21 and phosphorylated extracellular signal-regulated kinase (ERK) and decreased levels of Survivin and the 'split ends' (SPEN) protein family member RBM15.
We conclude that increased Msx2 expression results in improved outcome for breast cancer patients, possibly by increasing the likelihood of tumour cell death by apoptosis.
含有同源盒结构域的转录因子肌肉节同源盒 2（Msx2）在乳腺发育中发挥重要作用。然而，Msx2 在乳腺癌中的表达的临床意义尚不清楚。本研究旨在探讨 Msx2 作为乳腺癌生物标志物的潜在临床价值，并阐明其在体外的功能作用。
首先在经过充分验证的 295 例乳腺癌转录组数据集检查 Msx2 基因表达。然后通过包含 281 例浸润性乳腺癌的组织微阵列（TMA）评估 Msx2 蛋白表达。最后，为了评估 Msx2 在体外的功能作用，将 Msx2 异位表达于高侵袭性乳腺癌细胞系（MDA-MB-231）和永生化乳腺细胞系（MCF10a）中，并检测这些细胞系在生长速度、细胞死亡和细胞信号方面的变化。
在乳腺癌转录组数据集中检查 Msx2 mRNA 表达表明，Msx2 水平升高与预后良好相关（P=0.011）。在 TMA 上评估 Msx2 蛋白表达显示，Msx2 可在肿瘤细胞核和细胞质中检测到。细胞质 Msx2 表达与低级别肿瘤相关（P=0.012）和 Ki67 阴性相关（P=0.018）。核 Msx2 与低级别肿瘤相关（P=0.015）、雌激素受体阳性（P=0.038）、低 Ki67（P=0.005）和高 cyclin D1 表达相关（P=0.037）。细胞质 Msx2 表达增加与乳腺癌特异性生存（P=0.049）、无复发生存（P=0.029）和总生存（P=0.019）延长相关。在乳腺细胞系中外源表达 Msx2 导致细胞活力显着降低，介导细胞通过凋亡死亡。对表达 Msx2 的细胞的进一步分析显示，p21 和磷酸化细胞外信号调节激酶（ERK）水平升高，Survivin 和“分裂末端”（SPEN）蛋白家族成员 RBM15 水平降低。
我们得出结论，增加 Msx2 表达可改善乳腺癌患者的预后，可能通过增加细胞凋亡导致肿瘤细胞死亡的可能性。
Zotero 插件
