Unidad de Investigacion en Enferemedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, SSa, Mexico.
BMC Cancer. 2011 Jun 21;11:259. doi: 10.1186/1471-2407-11-259.
Raf-1 kinase inhibitor protein (RKIP) has been reported to negatively regulate signal kinases of major survival pathways. RKIP activity is modulated in part by phosphorylation on Serine 153 by protein kinase C, which leads to dissociation of RKIP from Raf-1. RKIP expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. The prognostic power has typically been based on total RKIP expression and has not considered the significance of phospho-RKIP.
The present study examined the expression levels of both RKIP and phospho-RKIP in human lung cancer tissue microarray proteomics technology.
Total RKIP and phospho-RKIP expression levels were similar in normal and cancerous tissues. phospho-RKIP levels slightly decreased in metastatic lesions. However, the expression levels of phospho-RKIP, in contrast to total RKIP, displayed significant predictive power for outcome with normal expression of phospho-RKIP predicting a more favorable survival compared to lower levels (P = 0.0118); this was even more pronounced in more senior individuals and in those with early stage lung cancer.
This study examines for the first time, the expression profile of RKIP and phospho-RKIP in lung cancer. Significantly, we found that phospho-RKIP was a predictive indicator of survival.
Raf-1 激酶抑制剂蛋白（RKIP）已被报道可负调控主要生存途径的信号激酶。RKIP 的活性部分受蛋白激酶 C 磷酸化丝氨酸 153调节，这导致 RKIP 与 Raf-1 解离。许多人类癌症中 RKIP 的表达水平较低，代表预后不良和/或诱导转移的指标。预测能力通常基于总 RKIP 表达，而未考虑磷酸化 RKIP 的意义。
本研究使用人类肺癌组织微阵列蛋白质组学技术检测了 RKIP 和磷酸化 RKIP 的表达水平。
正常组织和癌组织中的总 RKIP 和磷酸化 RKIP 表达水平相似。磷酸化 RKIP 在转移性病变中略有降低。然而，与总 RKIP 相比，磷酸化 RKIP 的表达水平具有显著的预后预测能力，正常表达的磷酸化 RKIP 预测生存更有利（P=0.0118）；在年龄较大的个体和早期肺癌患者中更为明显。
本研究首次检测了肺癌中 RKIP 和磷酸化 RKIP 的表达谱。重要的是，我们发现磷酸化 RKIP 是生存的预测指标。
