Overexpression of phosphatidylinositol 3-kinase in human lung cancer

Background: This study was conducted to investigate the expression of phosp hatidylinositol 3-kinase (PI3K) and AKT2, a downstream effector, in primary human lung carcinomas of different histological type. Methods: Specimens f rom 105 human lung carcinomas and their corresponding lymph nodes and liver metastases were examined using immunohistochemistry and Northern-blot assa ys to study the PI3K p85 and p110 subunits and the AKT2-expression patterns . Results: The p85 and p110 subunits of PI3K were overexpressed at the prot ein level in 77% and 59% of 80 primary lung carcinomas, respectively, irres pective of the histological type. PI3K overexpression was correlated with t umor grading. In contrast, no overexpression of PI3K subunits was observed in normal lung tissue and benign lung tumors. Consistent with these finding s, up-regulation of p110 mRNA transcripts was restricted to primary lung ca rcinomas. Overexpression of AKT2 was observed in 10% of the investigated lu ng tumor specimens, but in none of the healthy lung sections. A profound in crease of PI3K expression was uniformly observed in lung tissue specimens a nd in corresponding extra-pulmonary lymph-node and liver metastases with lo w-differentiation grades. Conclusion: PI3K appears to be associated with th e process of tumor-cell transformation and proliferation. One of its major downstream effector molecules, AKT2, which contributes to apoptotic cell de ath, was not upregulated by PI3K overexpression in primary lung carcinomas.