Lung Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Cancer, including details on symptoms, smoking, genetics, treatment, causes. | ||||||||
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Expression of alpha CP-4 inhibits cell cycle progression and suppresses tumorigenicity of lung cancer cells.Castaño Z, Vergara-Irigaray N, Pajares MJ, Montuenga LM, Pio R Division of Oncology, CIMA, University of Navarra, Pamplona, Spain. The protein alpha CP-4 (also known as hnRNP E4) is an RNA binding protein encoded by a gene at 3p21, one of the most common altered regions in lung cancer. It has been proposed that alpha CP-4 may function as a lung tumor suppressor. Lack of alpha CP-4 expression is frequent in highly proliferative lung tumors and correlates with alpha CP-4 allele losses. The aim of this study was to evaluate the effect of alpha CP-4 on the tumorigenic capacity of lung cancer cells. alpha CP-4 expression was induced by transient transfection or stable infection with recombinant retroviruses. Induction of alpha CP-4 expression caused cell cycle arrest in G(2)/M in 3 out of the 7 lung cancer cell lines studied, while no effect on apoptosis was observed. Anchorage-independent growth and invasion capacity of H1299 cells were significantly reduced by alpha CP-4 induction. Tumorigenicity of H1299 cells in nude mice was greatly inhibited by the expression of alpha CP-4. Moreover, induction of alpha CP-4 expression in already established tumors resulted in a sudden growth arrest. Immunocytochemistry analysis of the xenograft tumors revealed an in vivo effect of alpha CP-4 on cell proliferation and no effect on apoptosis. Finally, alpha CP-4 showed a subcellular localization different from alpha CP-4a, a splice variant that does not affect cell proliferation. In conclusion, expression of alpha CP-4 can inhibit proliferation and tumorigenesis of lung cancer cells, both in vivo and in vitro, by delaying the progression of the cell cycle. Published 4 February 2008 in Int J Cancer, 122(7): 1512-20.
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