Early Involvement of the Phosphatidylinositol 3-Kinase/Akt Pathway in Lung Cancer Progression

Signaling through the phosphatidylinositol 3-kinase (PI3-kinase) pathway has been associated with lung tumorigenesis. We examined the association between gene copy number of the PI3-kinase catalytic subunit alpha (PIK3CA) and phosphorylated Akt expression in invasive and preinvasive lung cancers. We...

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Bibliographic Details
Published in:	American journal of respiratory and critical care medicine Vol. 170; no. 10; pp. 1088 - 1094
Main Authors:	Massion, Pierre P, Taflan, Peter M, Shyr, Yu, Rahman, S. M. Jamshedur, Yildiz, Pinar, Shakthour, Bashar, Edgerton, Mary E, Ninan, Matthew, Andersen, Jeremiah J, Gonzalez, Adriana L
Format:	Journal Article
Language:	English
Published:	New York, NY Am Thoracic Soc 15-11-2004 American Lung Association American Thoracic Society
Subjects:	Aged Aged, 80 and over Analysis of Variance Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Biological and medical sciences Biomarkers, Tumor - metabolism Biopsy, Needle Clinical death. Palliative care. Organ gift and preservation Disease Progression Enzyme Activation Female Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Intensive care medicine Lung Neoplasms - enzymology Lung Neoplasms - genetics Lung Neoplasms - mortality Male Medical sciences Middle Aged Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Pneumology Probability Prognosis Proportional Hazards Models Risk Assessment Sampling Studies Sensitivity and Specificity Tissue Culture Techniques Tumors of the respiratory system and mediastinum Lung disease Intensive care Respiratory disease Enzyme tissue microarray Transferases Lung cancer PKB preinvasive Bronchopulmonary malignant tumor Amplification Kinase Bronchus disease tumorigenesis Resuscitation
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Summary:	Signaling through the phosphatidylinositol 3-kinase (PI3-kinase) pathway has been associated with lung tumorigenesis. We examined the association between gene copy number of the PI3-kinase catalytic subunit alpha (PIK3CA) and phosphorylated Akt expression in invasive and preinvasive lung cancers. We sought to determine at what stage of tumor development gene copy number increase or phosphorylated Akt overexpression might affect tumor development. We assessed PIK3CA gene copy number by fluorescence in situ hybridization and expression of phosphorylated Akt by immunohistochemistry in 242 invasive and 43 preinvasive lung cancers and correlated our findings with clinical outcome. The PIK3CA was amplified in 70% of squamous carcinomas, 38% of large cell carcinomas, 19% of adenocarcinomas, and 67% of small cell lung cancers. Phosphorylated Akt overexpression was frequently observed, and strongly so in 12 to 17% of lung cancers depending on nuclear or cytoplasmic localization. Neither PIK3CA gene copy number nor phosphorylated Akt protein expression had prognostic significance. In preinvasive lesions, amplification of the PIK3CA and overexpression of phosphorylated Akt were associated with severe dysplasia and each other. These observations suggest frequent and early involvement of the PI3-kinase pathway in lung cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1073-449X 1535-4970
DOI:	10.1164/rccm.200404-487OC