[Current views on the mechanism of oncogenic cell transformation in ovine pulmonary adenocarcinoma].
Lung cancer is the most frequently diagnosed of all the human neoplasms leading to death. Because twenty percent of cases are not associated with cigarette smoking, other causes and methods of early diagnosis are being sought. Bronchioloalveolar cancer, which is a subtype of the most common primary lung cancer, adenocarcinoma, is very similar to ovine pulmonary adenocarcinoma (OPA), a naturally occurring lung cancer in sheep. OPA is caused by the virus Jaagsiekte Sheep Retrovirus (JSRV), a member of the genus of beta-retroviruses. The virus induces neoplastic transformation of secretory epithelial cells of the lung, i.e. alveolar type II pneumocytes and Clara cells. JSRV's tropism for these cells is connected with viral LTR regions interacting with cellular factors that play major roles in the expression of lung-specific genes, e.g. those of surfactant proteins. Results of studies on the mechanisms of viral mutagenesis indicate a viral envelope protein (Env) as an oncogenic factor. There are two main enzymatic pathways involved in the cell transformation: PI3K-Akt and Ras-MEK-MAPK, both activated by the cytoplasmic tail of the envelope protein. Tumor development is associated with telomerase activation. Insertional mutagenesis has also been suggested because there is at least one common integration site for JSRV in OPA. Morphological and histological similarities with human bronchioloalveolar cancer and the possibility of experimental induction of the tumor in animals makes OPA a good model for the study of oncogenesis and target therapy of lung adenocarcinoma.
Kycko
Anna
A
Zakład Anatomii Patologicznej Państwowego Instytutu Weterynaryjnego - Państwowego Instytutu Badawczego w Puławach. anna.kycko@piwet.pulawy.pl
Reichert
Michał
M
D000230:Adenocarcinoma / Q000662:veterinary* / Q000821:virology*; D000818:Animals; D002472:Cell Transformation, Viral; D004195:Disease Models, Animal; D006801:Humans; D022141:Jaagsiekte sheep retrovirus / Q000472:pathogenicity; D008175:Lung Neoplasms / Q000662:veterinary* / Q000821:virology*; D011648:Pulmonary Adenomatosis, Ovine / Q000503:physiopathology* / Q000821:virology; D012756:Sheep; D019098:Telomerase
D019098:Telomerase