Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
J Clin Invest. 2010 Dec;120(12):4289-302. doi: 10.1172/JCI42015. Epub 2010 Nov 8.
The Pit-1 transcription factor (also know as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. Some of these protumorigenic effects of Pit-1 were mediated by upregulation of Snai1, an inductor of the epithelial-mesenchymal transition. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumor, high expression of Pit-1 was significantly correlated with Snai1 positivity. Notably, in these patients elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node-positive breast cancer and may represent a new therapeutic target.
Pit-1 转录因子（也称为 POU1F1）在哺乳动物前垂体器官发生过程中的细胞分化中发挥着关键作用，是垂体基因转录的转录激活剂。在人类致瘤性乳腺细胞中，已经报道了 Pit-1 的表达增加。在这里，我们发现人类乳腺癌细胞系中 Pit-1 的过表达或敲低诱导了与细胞增殖、凋亡和侵袭相关的蛋白表达的显著表型变化。Pit-1 的一些促瘤作用是通过上调 Snai1 介导的，Snai1 是上皮-间充质转化的诱导剂。在免疫缺陷小鼠中，Pit-1 的过表达诱导肿瘤生长并促进肺转移。在患有浸润性导管癌和淋巴结阳性肿瘤的患者中，Pit-1 的高表达与 Snai1 阳性显著相关。值得注意的是，在这些患者中，Pit-1 的高表达与远处转移的发生显著相关且独立。这些发现表明，Pit-1 可能有助于对淋巴结阳性乳腺癌患者做出更准确的预后判断，并且可能代表一个新的治疗靶点。
