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1 UMR754 Retroviruses and Comparative Pathology INRA, University of Lyon I, National Veterinary School, EPHE, IFR128 Biosciences Lyon-Gerland, and Depts of 2 Respiratory Diseases, Reference Centre for Orphan Lung Diseases, and 3 Pathology, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France.
CORRESPONDENCE: V. Cottin, UMR754, Lyon Gerland, Université Lyon I, 50 avenue Tony Garnier, 69007 Lyon, France, Fax: 33 437287605. E-mail: vincent.cottin{at}chu-lyon.fr
Keywords: Akt, bronchioloalveolar carcinoma, jaagsiekte sheep retrovirus, lung cancer, telomerase, type-II pneumocyte
Received: October 26, 2005
Accepted January 23, 2006
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.
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