Sizova Daria, Ho Yugong, Cooke Nancy E, Liebhaber Stephen A
Room 560A Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Mol Endocrinol. 2010 Nov;24(11):2232-40. doi: 10.1210/me.2010-0235. Epub 2010 Sep 9.
We report the establishment of three distinct pituitary-derived murine cell lines generated by targeted T-antigen-induced transformation. The Pit1/0 line expresses pituitary-specific transcription factor-1 (Pit-1) but lacks expression of GH, prolactin (Prl), or TSH, and the Pit1/Prl line is selectively positive for Pit-1 and Prl. The third line, Pit1/Triple, expresses Pit-1 and all three of the Pit-1-dependent hormones: GH, Prl, and TSHβ/glycoprotein hormone α-subunit. The three corresponding transformation events appear to have captured pituitary cells representing: 1) an initial step in the Pit-1(+) lineage, 2) a cell line that corresponds to the differentiated lactotrope, and 3) a novel tri-hormone intermediate that may represent a pivotal step in Pit-1(+) cell lineage differentiation. The documented dependence of the tri-hormone expression in the Pit-1/Triple line on Pit-1 activity supports its potential role in the pathway of pituitary cell differentiation. The presence of a 123-kb human transgene encompassing the hGH locus (hGH/bacterial artificial chromosome) in two of these lines, Pit1/0 and Pit1/Prl, further expands their potential utility to the analysis of gene activation within the hGH gene cluster.
我们报告了通过靶向T抗原诱导转化建立的三种不同的源自垂体的小鼠细胞系。Pit1/0细胞系表达垂体特异性转录因子-1(Pit-1),但缺乏生长激素(GH)、催乳素(Prl)或促甲状腺激素(TSH)的表达,而Pit1/Prl细胞系对Pit-1和Prl呈选择性阳性。第三种细胞系Pit1/Triple表达Pit-1以及所有三种依赖于Pit-1的激素:GH、Prl和TSHβ/糖蛋白激素α亚基。这三种相应的转化事件似乎捕获了代表以下情况的垂体细胞:1)Pit-1(+)谱系中的初始步骤;2)对应于分化的催乳素细胞的细胞系;3)一种新型的三激素中间体,可能代表Pit-1(+)细胞谱系分化中的关键步骤。Pit1/Triple细胞系中三激素表达对Pit-1活性的记录依赖性支持了其在垂体细胞分化途径中的潜在作用。在其中两个细胞系Pit1/0和Pit1/Prl中存在包含hGH基因座的123 kb人类转基因(hGH/细菌人工染色体),进一步扩展了它们在分析hGH基因簇内基因激活方面的潜在用途。