Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
Cell Cycle. 2010 Aug 1;9(15):3119-26. doi: 10.4161/cc.9.15.12526.
Human PTE Fb is a protein kinase composed by CDK9 and Cyclin T that controls the elongation phase of RNA Pol II. This complex also affects the activation and differentiation program of lymphoid cells. In this study we found that several head and neck tumor cell lines overexpress PTE Fb. We also established that Cyclin T1 is able to induce transformation in vitro, as we determined by foci and colony formation assays. Nu/nu mice s.c. injected with stable transfected Cyclin T1 cells (NIH 3T3 Cyclin T1) developed tumors faster than animals injected with control cells (NIH 3T3 beta-gal). In vitro, NIH 3T3 Cyclin T1 cells show increased proliferation and CDK4-Rb phosphorylation. Even more, silencing E2F1 expression (shRNA E2F1) in NIH 3T3 cells resulted in a dramatic inhibition of Cyclin T1-induced foci. All these data demonstrate for the first time the Cyclin T1 oncogenic function and suggest a role for this protein in controlling cell cycle probably via Rb/E2F1 pathway.
人 PTE Fb 是一种由 CDK9 和 Cyclin T 组成的蛋白激酶，它控制着 RNA Pol II 的延伸阶段。该复合物还影响淋巴样细胞的激活和分化程序。在这项研究中，我们发现一些头颈部肿瘤细胞系过度表达 PTE Fb。我们还确定 Cyclin T1 能够在体外诱导转化，我们通过焦点和集落形成测定来确定。皮下注射稳定转染 Cyclin T1 细胞（NIH 3T3 Cyclin T1）的裸鼠比注射对照细胞（NIH 3T3 beta-gal）的动物更快地发展为肿瘤。在体外，NIH 3T3 Cyclin T1 细胞显示出增殖和 CDK4-Rb 磷酸化增加。甚至，沉默 NIH 3T3 细胞中的 E2F1 表达（shRNA E2F1）导致 Cyclin T1 诱导的焦点显著抑制。所有这些数据首次证明了 Cyclin T1 的致癌功能，并提示该蛋白可能通过 Rb/E2F1 途径控制细胞周期。
