乳腺癌患者的预后情况如何直接与肿瘤转移的程度相关。然而，上皮型肿瘤细胞脱离原发肿瘤组织，转移至远端器官形成克隆转移灶的确切机制至今不甚明了。
近来，刊登在The Journal of Biological Chemistry杂志上的一则研究着重探究分析了乳腺癌肿瘤组织中垂体瘤转化基因1（PTTG1）的表达水平，这个基因是一个相对未知的蛋白，研究人员将肿瘤患者源性乳房癌组织与相应的正常乳腺组织相比较，结果发现与正常组织相比，PTTG1高表达于乳腺癌患者中。
此外，PTTG1的表达水平与乳腺癌细胞株的恶性程度呈正相关性，迁移浸润性能高的肿瘤细胞株MDA-MB-231和BT54高表达PTTG1，而迁移侵袭能力较弱的MCF7、SK- BR3以及正常MCF10A细胞株低表达PTTG1。
通过调控PTTG1的表达水平，研究人员发现PTTG1能通过调控上皮/间质细胞标志物的表达、上调转录因子Snail来诱导上皮间质转化，改变肿瘤细胞形态以提高乳腺癌细胞的迁移和侵袭特性。值得注意的是，PTTG1下调能通过减少肿瘤细胞自我更新能力和致瘤能力，抑制BT549细胞癌症干细胞的数量，同时CD44高表达以及CD24低表达的细胞株数量也会降低，Sox2的表达也出现降低现象。
进一步研究证实PTTG1介导恶性肿瘤的特性部分是通过活化AKT来完成的，AKT是肿瘤细胞EMT和维持肿瘤细胞干细胞样特性的关键调节因子。总的来说，这些研究院结果表明PTTG1可能是一个恶性乳腺癌新的治疗靶点。（生物谷：Bioon.com）
doi:10.1074/jbc.M111.337428
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PTTG1 Oncogene Promotes Tumor Malignancy via Epithelial to Mesenchymal Transition and Expansion of Cancer Stem Cell Population*
Chang-Hwan Yoon, Min-Jung Kim, Hyejin Lee, Rae-Kwon Kim, Eun-Jung Lim, Ki-Chun Yoo,et al.
The prognosis of breast cancer patients is related to the degree of metastasis. However, the mechanisms by which epithelial tumor cells escape from the primary tumor and colonize at a distant site are not entirely understood. Here, we analyzed expression levels of pituitary tumor-transforming gene-1 (PTTG1), a relatively uncharacterized oncoprotein, in patient-derived breast cancer tissues with corresponding normal breast tissues. We found that PTTG1 is highly expressed in breast cancer patients, compared with normal tissues. Also, PTTG1 expression levels were correlated with the degree of malignancy in breast cancer cell lines; the more migratory and invasive cancer cell lines MDA-MB-231 and BT549 displayed the higher expression levels of PTTG1 than the less migratory and invasive MCF7 and SK-BR3 and normal MCF10A cell lines. By modulating PTTG1 expression levels, we found that PTTG1 enhances the migratory and invasive properties of breast cancer cells by inducing epithelial to mesenchymal transition, as evidenced by altered morphology and epithelial/mesenchymal cell marker expression patterns and up-regulation of the transcription factor Snail. Notably, down-regulation of PTTG1 also suppressed cancer stem cell population in BT549 cells by decreasing self-renewing ability and tumorigenic capacity, accompanying decreasing CD44high CD24low cells and Sox2 expression. Up-regulation of PTTG1 had the opposite effects, increasing sphere-forming ability and Sox2 expression. Importantly, PTTG1-mediated malignant tumor properties were due, at least in part, to activation of AKT, known to be a key regulator of both EMT and stemness in cancer cells. Collectively, these results suggest that PTTG1 may represent a new therapeutic target for malignant breast cancer.
