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Expression of αCP‐4 inhibits cell cycle progression and suppresses tumorigenicity of lung cancer cells
Author(s) -
Castaño Zafira,
VergaraIrigaray Nuria,
Pajares Maria J.,
Montuenga Luis M.,
Pio Ruben
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23236
Subject(s) - carcinogenesis , lung cancer , cancer research , cell cycle , biology , cell growth , apoptosis , transfection , alpha (finance) , microbiology and biotechnology , cancer , cell cycle checkpoint , cell culture , pathology , medicine , genetics , biochemistry , construct validity , nursing , patient satisfaction
The protein αCP‐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 αCP‐4 may function as a lung tumor suppressor. Lack of αCP‐4 expression is frequent in highly proliferative lung tumors and correlates with αCP‐4 allele losses. The aim of this study was to evaluate the effect of αCP‐4 on the tumorigenic capacity of lung cancer cells. αCP‐4 expression was induced by transient transfection or stable infection with recombinant retroviruses. Induction of αCP‐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 αCP‐4 induction. Tumorigenicity of H1299 cells in nude mice was greatly inhibited by the expression of αCP‐4. Moreover, induction of αCP‐4 expression in already established tumors resulted in a sudden growth arrest. Immunocytochemistry analysis of the xenograft tumors revealed an in vivo effect of αCP‐4 on cell proliferation and no effect on apoptosis. Finally, αCP‐4 showed a subcellular localization different from αCP‐4a, a splice variant that does not affect cell proliferation. In conclusion, expression of αCP‐4 can inhibit proliferation and tumorigenesis of lung cancer cells, both in vivo and in vitro , by delaying the progression of the cell cycle. © 2007 Wiley‐Liss, Inc.