Telomerase activation in a model of lung adenocarcinoma

• Published in: The European respiratory journal Vol. 27; no. 6; pp. 1175 - 1182
• Main Authors: Suau, F, Cottin, V, Archer, F, Croze, S, Chastang, J, Cordier, G, Thivolet-Bejui, F, Mornex, J-F, Leroux, C
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01.06.2006; Maney; European Respiratory Society
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma, Bronchiolo-Alveolar - genetics; Adenocarcinoma, Bronchiolo-Alveolar - pathology; Animals; Biological and medical sciences; Cell Division - genetics; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; Cellular Senescence - genetics; Disease Models, Animal; Enzyme Activation - genetics; Gene Expression Regulation - genetics; Humans; Jaagsiekte sheep retrovirus - genetics; Life Sciences; Lung - pathology; Lung Neoplasms - genetics; Medical sciences; Pneumology; Proto-Oncogene Proteins c-akt - genetics; Pulmonary Adenomatosis, Ovine - genetics; Pulmonary Alveoli - pathology; Sheep; Signal Transduction - genetics; Telomerase - genetics; Tumor Cells, Cultured - pathology; Tumors of the respiratory system and mediastinum; Lung disease; jaagsiekte sheep retrovirus; Respiratory disease; Enzyme; Lung cancer; Activation; Malignant tumor; Akt; Bronchopulmonary adenocarcinoma; type-ll pneumocyte; bronchioloalveolar carcinoma; Bronchus disease; Models; Telomerase; akt; lung cancer; telomerase; type-II pneumocyte
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.06.00125105

Ovine pulmonary adenocarcinoma (OPA) is a lung cancer strikingly similar to the pneumonic-type mixed invasive adenocarcinoma with a predominant bronchioloalveolar component in humans. Telomerase activity in OPA and the potential involvement of the kinase Akt in telomerase activation and regulation of cell proliferation were investigated. Lung tissues were collected from sheep with a histopathological diagnosis of OPA or controls. Epithelial cell cultures were derived in vitro from lung tissues. Telomerase activity was evaluated using the telomeric repeat amplification protocol method. Phosphorylation of Akt was detected by Western blotting. Telomerase activity was significantly higher in OPA lung tissues compared to control lung tissues. A high telomerase activity was detected in eight out of 12 (67%) primary cell cultures derived from tumours. A high level of expression of phosphorylated Akt was found in 10 out of 27 (37%) tumours, with abolition of Akt activation in response to epidermal growth factor stimulation demonstrated in primary cell cultures derived from tumours. Telomerase activation takes place in ovine pulmonary adenocarcinoma tumour cells and may be partly attributable to Akt activation. Telomerase may inhibit cellular senescence and contribute to the accumulation of tumour cells in mixed adenocarcinoma with a bronchioloalveolar component. Further work is necessary to identify alternative signalling pathways of telomerase activation in tumours.