Funcion de alfacp4 en la carcinogenesis pulmonar evaluacion de su posible papel como gen supresor de tumores

Abstract

ROLE OF alphaCP-4, A PUTATIVE TUMOR SUPPRESSOR GENE,IN LUNG CÁNCER. Zafira Castaño Corsino Faculty of Science University of Navarra, 2006 aCP-4 is an rna binding protein coded by a gene at 3p21. It has been proposed that aCP-4 may function as a "lung tumor suppressor gene. Lack of aCP-4 expression is freqüent in highly proliferative lung tumors. This activity is not observed in aCP-4a, a splice variant whose expression is apparently normal in lung tumors. The aims of this study were to evalúate the relationship between aCP-4 expression and survival of patients affected with lung cáncer, study the induction of aCP-4 expression by p53, evalúate the efrect of aCP-4 and aCP-4a in the tumorigenic capacity of lung cáncer cells and study the proliferation status of H1299 lung cáncer cell unes when they are treated with chemotherapic drugs and aCP-4 is expressed. No relationship was found between aCP-4 expression and survival. By inducing damages in the DNA we could see that aCP-4 expression was induced by r>53. Employing transient transfection in different lung cáncer cell lines as well as infection with recombinant retroviruses in H1299 cells aCP-4 and aCP-4a expression was induced. A different subcellular localization of aCP-4 and aCP-4a was observed that could account for their different effects on cell proliferation, cell cycle arrest in G2/M, suppression of anchorage-independent growth in soft agar and reduction of the invasión capacity. Finally, tumorigenicity of H1299 cells in nude mi ce was greatly inhibited by expression of aCP-4. in conclusión, expression of aCP-4 is induced by p53 and can inhibit proliferation and tumorigénesis of H1299 cells by inducing cell cycle arrest. These results suggest that aCP-4 inactivation may be an important event in the early stages of lung carcinogenesis.