Institute of Pathology Charité, University Hospital Berlin, 10117 Berlin, Germany.
Diagn Pathol. 2014 Apr 16;9:82. doi: 10.1186/1746-1596-9-82.
3-phosphoinositide-dependent protein kinase-1 (PDK1) functions downstream of phosphoinositide 3-kinase (PIK3) and activates members of the AGC family of protein kinases that are known to play crucial roles in physiological processes associated with cell metabolism, growth, proliferation and survival. Changes in the expression and activity of PDK1 and several AGC kinases have been linked to human disease, including cancer.
We used immunohistochemical analysis to determine PDK1 expression in 241 tumors from patients with breast cancer in which we had previously analyzed PIK3CA mutation status.
Moderate or high expression of PDK1 was observed in 213 of the 241 cases (88%). There was no correlation between PIK3CA mutation status and PDK1 overexpression.
Our findings indicate that PDK1 is independently activated in breast cancer and not only as part of the PIK3CA pathway, suggesting that PDK1 plays a specific and distinct role from the canonical PIK3/Akt pathway and promotes oncogenesis independently of AKT. Our data implicate PDK-1 and downstream components of the PDK-1 signaling pathway as promising therapeutic targets for the treatment of breast cancer.
3-磷酸肌醇依赖性蛋白激酶-1（PDK1）是磷酸肌醇 3-激酶（PI3K）的下游因子，可激活 AGC 蛋白激酶家族成员，这些激酶在与细胞代谢、生长、增殖和存活相关的生理过程中发挥着关键作用。PDK1 和几种 AGC 激酶的表达和活性变化与人类疾病有关，包括癌症。
我们使用免疫组织化学分析方法检测了 241 例乳腺癌患者肿瘤组织中 PDK1 的表达情况，这些患者的 PIK3CA 突变状态之前已进行了分析。
在 241 例病例中，有 213 例（88%）观察到 PDK1 中度或高度表达。PDK1 过表达与 PIK3CA 突变状态之间无相关性。
我们的研究结果表明，PDK1 在乳腺癌中独立激活，不仅是 PIK3CA 通路的一部分，这表明 PDK1 发挥了特定且独特的作用，不同于经典的 PI3K/Akt 通路，并独立于 AKT 促进肿瘤发生。我们的数据表明 PDK-1 及其下游信号通路组件是治疗乳腺癌的有前途的治疗靶点。
