Tobacco carcinogen-induced cellular transformation increases activation of the phosphatidylinositol 3'-kinase/Akt pathway in vitro and in vivo

The role of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway during tobacco carcinogen-induced transformation is unknown. To address this question, we evaluated this pathway in isogenic immortalized or tumorigenic human bronchial epithelial cells in vitro, as well as in progressive murine...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-01, Vol.64 (2), p.446-451
Main Authors: WEST, Kip A, LINNOILA, Ilona R, BELINSKY, Steven A, HARRIS, Curtis C, DENNIS, Phillip A
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Carcinogens - toxicity
Cell Line
Cell Line, Tumor
Cell Transformation, Neoplastic - drug effects
Enzyme Activation
Humans
Lung
Lung Neoplasms - enzymology
Lung Neoplasms - pathology
Medical sciences
Mice
Nicotiana - adverse effects
Pharmacology. Drug treatments
Phosphatidylinositol 3-Kinases - metabolism
Precancerous Conditions - enzymology
Precancerous Conditions - pathology
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Respiratory Mucosa
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The role of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway during tobacco carcinogen-induced transformation is unknown. To address this question, we evaluated this pathway in isogenic immortalized or tumorigenic human bronchial epithelial cells in vitro, as well as in progressive murine lung lesions induced by a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Compared with immortalized cells, tumorigenic cells had greater activation of the PI3K/Akt pathway, enhanced survival, and increased apoptosis in response to inhibition of the pathway. In vivo, increased activation of Akt and mammalian target of rapamycin was observed with increased phenotypic progression. Collectively, these results support the hypothesis that maintenance of Akt activity is necessary for survival of preneoplastic as well as transformed lung epithelial cells and suggest that inhibition of the PI3K/Akt pathway might be a useful approach to arrest lung tumorigenesis.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-03-3241