磷脂酰肌醇3-激酶在人乳腺癌中的活化

背景与目的：磷脂酰肌醇3-激酶（phosphatidylinsitol 3-kinase,P13-K)可被多种有丝分裂信号刺激活化,它参与有关细胞生长信号的调控,但其在人类肿瘤中的作用尚不清楚。本研究旨在探讨人乳腺癌中P13-K的蛋白表达、mRNA表达和激酶活性变化情况。方法：应用Western blot、免疫沉淀、激酶活性测定和RT-PCR方法检测了37例人乳腺癌及其周围非癌组织中P13-KP85亚单位的表达及P13-K活性变化。结果：与周围非癌组织相比,37例人乳腺癌中,32例（86.49%)P13-Kp85亚单位蛋白表达显著增加;35例（94.59%)P13-Kp85亚单位mRNA水平明显增高;25例（67.57%)p13-k激酶活性亦显著增高。结论：人乳腺癌中P13-K被活化,提示P13-K参与乳腺癌细胞的信号转导;它有可能成为人乳腺癌治疗的新靶点。

Activation of phosphatidylinositol 3-kinase in human breast carcinoma

Background &Objective:Phosphatidylinositol 3-kinase(PI3-K)has been implicated in the signaling pathways regulating cell growth by v irtue of its activation in response t o various mitogenic stimuli,but the role of PI3-K in human tumorigenesis has not yet to be defined.This study was designed to i nvestigate the levels of both PI3-K p rotein and PI3-K mRNA and the activity of PI3-K i n human breast tumors.Methods :Western blot,immunoprecipitation,kinase activity assay,and RT-PCR were used to detect the expression and activit y of PI3-K in 37patients with breast c ancers.Results:Significantly increased expressio n of p85subunit of PI3-K at levels of both protein and mRNA were found in 32(86.49%)and 35(94.59%)out of the 37breast tumors compared with adjacent normal tissue.Signifi cantly higher level of the activity of PI3-kinase was observed in 25(67.57%)out of the 37cases.Conclusions :PI3-K was highly activated in breast tumor tissue compared with ad jacent normal tissue,suggesting th at PI3-K was involved in the signal tr ansduction of breast tumorigenesis.It may be a potential target for new strategies for the treatment of the patients with br east cancers.