Wiegering Armin, Pfann Christina, Uthe Friedrich Wilhelm, Otto Christoph, Rycak Lukas, Mäder Uwe, Gasser Martin, Waaga-Gasser Anna-Maria, Eilers Martin, Germer Christoph-Thomas
Department of General, Visceral, Vascular and Paediatric Surgery (Department of Surgery I), University Hospital Wuerzburg, Wuerzburg, Germany ; Department of Biochemistry and Molecular Biology, University of Wuerzburg, Wuerzburg, Germany.
PLoS One. 2013 Oct 1;8(10):e75292. doi: 10.1371/journal.pone.0075292. eCollection 2013.
The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.
蛋白磷酸酶2A的癌性抑制剂（CIP2A）是一种使c-Myc蛋白稳定的致癌因子。CIP2A在多种肿瘤中过表达，其表达水平是长期预后的独立标志物。为了确定CIP2A在结肠癌中表达是否升高以及它是否可作为生存的预后标志物，我们通过实时PCR分析了104例结肠癌样本中CIP2A mRNA的表达。CIP2A mRNA在结肠癌样本中过表达，且CIP2A表达水平与肿瘤分期显著相关。我们发现CIP2A可作为无病生存期和总生存期的独立预后标志物。此外，我们通过使用小干扰（si）RNA和短发夹（sh）RNA沉默CIP2A，研究了CIP2A对三种结肠癌细胞系中c-Myc、Akt水平及细胞增殖的依赖性影响。CIP2A的缺失显著抑制结肠癌细胞系的生长并降低c-Myc水平，而不影响上游调节激酶Akt的表达或功能。发现CIP2A的表达依赖于MAPK活性，将结肠癌中升高的c-Myc表达与失调的信号转导联系起来。
