Sahoo Sunati, Brickley Deanna R, Kocherginsky Masha, Conzen Suzanne D
Department of Pathology, University of Louisville, Louisville, KY 40202, USA.
Eur J Cancer. 2005 Nov;41(17):2754-9. doi: 10.1016/j.ejca.2005.07.018. Epub 2005 Oct 24.
The phosphatidylinositol 3-kinase (PI3-K) signalling pathway has been implicated in breast cancer development and resistance to therapy. Akt-1 and serum and glucocorticoid-induced kinase-1 (SGK-1) are homologous kinases which are important downstream effectors of PI3-K signalling. We sought to determine the individual expression patterns of these two kinases in order to better understand their respective roles in PI3-K signalling in breast cancer. To this end, we examined the expression of both p-Akt-1 and SGK-1 in 40 breast cancers. p-Akt-1 expression was seen in 58% of tumour samples, while SGK-1 overexpression was detected in 48%. Interestingly, a highly significant association was found between the expression of p-Akt-1 and SGK-1 (P=0.002), suggesting complementary physiological functions in PI3-K signalling. This finding is consistent with recent genetic data from Caenorhabditis elegans suggesting that both SGK-1 and Akt-1 are required for signalling downstream of insulin receptor activation.
磷脂酰肌醇3激酶(PI3-K)信号通路与乳腺癌的发生发展及治疗耐药性有关。Akt-1和血清及糖皮质激素诱导激酶-1(SGK-1)是同源激酶,是PI3-K信号通路重要的下游效应器。我们试图确定这两种激酶的个体表达模式,以便更好地了解它们在乳腺癌PI3-K信号通路中的各自作用。为此,我们检测了40例乳腺癌中p-Akt-1和SGK-1的表达。在58%的肿瘤样本中可见p-Akt-1表达,而48%检测到SGK-1过表达。有趣的是,发现p-Akt-1和SGK-1的表达之间存在高度显著的相关性(P=0.002),提示在PI3-K信号通路中具有互补的生理功能。这一发现与秀丽隐杆线虫最近的遗传学数据一致,表明SGK-1和Akt-1都是胰岛素受体激活下游信号传导所必需的。