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-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.
Al-Wadei
H A N
HA
Experimental Oncology Laboratory, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Takahasi
T
T
Schuller
H M
HM
D000230:Adenocarcinoma / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D003907:Dexamethasone; D017868:Cyclic AMP-Dependent Protein Kinases