Telomerase activation in a model of lung adenocarcinoma

¹ UMR754 Rétrovirus et Pathologie Comparée INRA, Université Lyon I, Ecole Nationale Vétérinaire de Lyon, Ecole Pratique des Hautes Etudes, IFR128 Biosciences Lyon-Gerland
² UMR754 Rétrovirus et Pathologie Comparée INRA, Université Lyon I, Ecole Nationale Vétérinaire de Lyon, Ecole Pratique des Hautes Etudes, IFR128 Biosciences Lyon-Gerland; and Service de pneumologie - Centre des maladies orphelines pulmonaires, Hôpital Louis Pradel, Hospices Civils de Lyon
³ UMR754 Rétrovirus et Pathologie Comparée INRA, Université Lyon I, Ecole Nationale Vétérinaire de Lyon, Ecole Pratique des Hautes Etudes, IFR128 Biosciences Lyon-Gerland; and Service d'anatomie et cytologie pathologiques, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France.

^* To whom correspondence should be addressed. E-mail: vincent.cottin{at}chu-lyon.fr.

	Abstract

Ovine pulmonary adenocarcinoma (OPA) is a lung cancer strikingly similar to the pneumonic-type mixed invasive adenocarcinoma with a predominant bronchioloalveolar component in humans. We investigated telomerase activity in OPA and the potential involvement of the kinase Akt in telomerase activation and regulation of cell proliferation.

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 by the Telomeric Repeat Amplification Protocol method. Phosphorylation of Akt was detected by western-blotting.

Telomerase activity was significantly higher in OPA lung tissues as compared with control lung tissues. A high telomerase activity was detected in 8/12 (67%) primary cell cultures derived from tumours. A high level of expression of phosphorylated Akt was found in 10/27 (37%) tumours, with abolition of Akt activation in response to EGF stimulation demonstrated in primary cell cultures derived from tumours.

Telomerase activation takes place in OPA 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 bronchioloalveolar component. Further work is necessary to identify alternative signalling pathways of telomerase activation in tumours.

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