Ski 蛋白水平在 HPV16 永生化人角质细胞体外进展和宫颈癌中增加。
Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer.
机构信息
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA.
出版信息
Virology. 2013 Sep;444(1-2):100-8. doi: 10.1016/j.virol.2013.05.039. Epub 2013 Jun 27.
We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer.
我们比较了 Ski 癌蛋白（一种转化生长因子-β（TGF-β）信号抑制剂）在正常人类角质细胞（HKc）、HPV16 永生化 HKc（HKc/HPV16）和分化抵抗的 HKc/HPV16（HKc/DR）中的水平，这些细胞在不存在和存在 TGF-β的情况下进行了比较。与 HKc 相比，HKc/HPV16 和 HKc/DR 中的 Ski 蛋白水平稳定增加。TGF-β 处理 HKc、HKc/HPV16 和 HKc/DR 显著降低了 Ski。HKc/DR 中的 Ski 降解延迟。Ski 和磷酸化 Ski 蛋白水平与细胞周期相关，在 G2/M 期间 Ski 表达和定位到中心体和有丝分裂纺锤体。在 HKc/DR 中，Ski 的 shRNA 敲低抑制了细胞增殖。与相邻正常组织相比，在宫颈癌组织阵列中，宫颈癌样本中 Ski 的核和细胞质染色更强烈，且 Ski 的定位发生改变。总的来说，这些研究表明 HPV16 转化的人类角质细胞和宫颈癌中 Ski 蛋白水平、降解和定位发生改变。
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