PKA-dependent growth stimulation of cells derived from human pulmonary adenocarcinoma and small airway epithelium by dexamethasone

Smoking is a risk factor for lung cancer, chronic obstructive pulmonary disease, chronic bronchitis and asthma. The chronic lung diseases are also a predisposing factor for the development of lung cancer. Glucocorticoids are used for the management of chronic lung diseases because of their anti-infl...

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Bibliographic Details
Published in:European journal of cancer (1990) 2005-11, Vol.41 (17), p.2745-2753
Main Authors: Al-Wadei, H.A.N., Takahasi, T., Schuller, H.M.
Format: Article
Language:English
Subjects:
Adenocarcinoma - pathology
Antineoplastic Agents - pharmacology
Biological and medical sciences
Bronchi - pathology
cAMP
Cell Line, Tumor
Cell proliferation
Cell Proliferation - drug effects
CREB
Cyclic AMP-Dependent Protein Kinases - pharmacology
Dexamethasone
Dexamethasone - pharmacology
Epithelial Cells - drug effects
Epithelial Cells - pathology
ERK1/2
Humans
Lung adenocarcinoma
Lung Neoplasms - pathology
Medical sciences
Pharmacology. Drug treatments
PKA
Respiratory Mucosa - drug effects
Respiratory Mucosa - pathology
Tumors
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Summary:Smoking is a risk factor for lung cancer, chronic obstructive pulmonary disease, chronic bronchitis and asthma. The chronic lung diseases are also a predisposing factor for the development of lung cancer. Glucocorticoids are used for the management of chronic lung diseases because of their anti-inflammatory activity. These drugs also have anti-tumourigenic effects in mouse models of lung cancer. Glucocorticoids are frequently used as co-treatment with cancer therapy. Using the human pulmonary adenocarcinoma (PAC) cell line NCI-H322 with features of bronchiolar Clara cells, and immortalised human small airway epithelial cells, our data show that the glucocorticoid dexamethasone increased cell proliferation in MTT assays in a PKA-dependent manner. Dexamethasone significantly increased intracellular cAMP in direct immunoassays. Immunoblot analysis revealed increased phosphorylation of ERK1/2 and of the transcription factor CREB in response to dexamethasone. These data suggest that glucocorticoids could have tumour promoting activity on a sub-set of human PAC.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2005.09.001