Overexpression of phosphatidylinositol 3-kinase in human lung cancer.
BACKGROUND
This study was conducted to investigate the expression of phosphatidylinositol 3-kinase (PI3K) and AKT2, a downstream effector, in primary human lung carcinomas of different histological type.


METHODS
Specimens from 105 human lung carcinomas and their corresponding lymph nodes and liver metastases were examined using immunohistochemistry and Northern-blot assays 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 protein level in 77% and 59% of 80 primary lung carcinomas, respectively, irrespective of the histological type. PI3K overexpression was correlated with tumor grading. In contrast, no overexpression of PI3K subunits was observed in normal lung tissue and benign lung tumors. Consistent with these findings, upregulation of p110 mRNA transcripts was restricted to primary lung carcinomas. Overexpression of AKT2 was observed in 10% of the investigated lung tumor specimens, but in none of the healthy lung sections. A profound increase of PI3K expression was uniformly observed in lung tissue specimens and in corresponding extra-pulmonary lymph-node and liver metastases with low-differentiation grades.


CONCLUSIONS
PI3K appears to be associated with the process of tumor-cell transformation and proliferation. One of its major downstream effector molecules, AKT2, which contributes to apoptotic cell death, was not upregulated by PI3K overexpression in primary lung carcinomas.
Lin
X
X
Department of General and Thoracic Surgery, University of Kiel, Arnold-Heller Strasse 7, 24105 Kiel, Germany. ffaendrich@surgery.uni-kiel.de
Böhle
A S
AS
Dohrmann
P
P
Leuschner
I
I
Schulz
A
A
Kremer
B
B
Fändrich
F
F
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015152:Blotting, Northern; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015854:Up-Regulation
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494921:AKT2 protein, human