INTRODUCTION: The expression, mechanisms of regulation, and functional impact of INHBA (activin A) in lung adenocarcinoma (AD) have not been fully elucidated. METHODS: INHBA expression was examined in 96 lung samples (86 ADs, 10 normal lung) using oligonucleotide microarrays and 187 lung samples (164 ADs, 6 bronchioalveolar carcinomas, and 17 normal lung) using immunohistochemistry. The proliferation of AD cell lines H460 and SKLU1 was examined with WST-1 assays after treatment with recombinant activin A, follistatin, and INHBA-targeting small-interfering RNA. Cells were also treated with 5-aza-2' deoxycytidine and trichostatin A to investigate the role of epigenetic regulation in INHBA expression. RESULTS: Primary ADs expressed 3.1 times more INHBA mRNA than normal lung. In stage I AD patients, high levels of primary tumor INHBA transcripts were associated with worse prognosis. Immunohistochemistry confirmed higher inhibin betaA protein expression in ADs (78.7%) and bronchioalveolar carcinomas (66.7%) compared with normal lung (11.8%). H460 and SKLU1 demonstrated increased proliferation when treated with exogenous activin A and reduced proliferation when treated with follistatin or INHBA-targeting small-interfering RNA. INHBA mRNA expression in H460 cells was upregulated after treatment with trichostatin A and 5-aza-2' deoxycytidine. CONCLUSIONS: INHBA is overexpressed in AD relative to controls. Inhibin betaA may promote cell proliferation, and its overexpression is associated with worse survival in stage I AD patients. In addition, overexpression of INHBA may be affected by promoter methylation and histone acetylation in a subset of lung ADs.
INTRODUCTION: The expression, mechanisms of regulation, and functional impact of INHBA (activin A) in lung adenocarcinoma (AD) have not been fully elucidated. METHODS:INHBA expression was examined in 96 lung samples (86 ADs, 10 normal lung) using oligonucleotide microarrays and 187 lung samples (164 ADs, 6 bronchioalveolar carcinomas, and 17 normal lung) using immunohistochemistry. The proliferation of AD cell lines H460 and SKLU1 was examined with WST-1 assays after treatment with recombinant activin A, follistatin, and INHBA-targeting small-interfering RNA. Cells were also treated with 5-aza-2' deoxycytidine and trichostatin A to investigate the role of epigenetic regulation in INHBA expression. RESULTS: Primary ADs expressed 3.1 times more INHBA mRNA than normal lung. In stage I ADpatients, high levels of primary tumorINHBA transcripts were associated with worse prognosis. Immunohistochemistry confirmed higher inhibin betaA protein expression in ADs (78.7%) and bronchioalveolar carcinomas (66.7%) compared with normal lung (11.8%). H460 and SKLU1 demonstrated increased proliferation when treated with exogenous activin A and reduced proliferation when treated with follistatin or INHBA-targeting small-interfering RNA. INHBA mRNA expression in H460 cells was upregulated after treatment with trichostatin A and 5-aza-2' deoxycytidine. CONCLUSIONS:INHBA is overexpressed in AD relative to controls. Inhibin betaA may promote cell proliferation, and its overexpression is associated with worse survival in stage I ADpatients. In addition, overexpression of INHBA may be affected by promoter methylation and histone acetylation in a subset of lung ADs.
Authors: Enoc M Cortés-Malagón; José Bonilla-Delgado; José Díaz-Chávez; Alfredo Hidalgo-Miranda; Sandra Romero-Cordoba; Aykut Uren; Haydar Celik; Matthew McCormick; José A Munguía-Moreno; Eloisa Ibarra-Sierra; Jaime Escobar-Herrera; Paul F Lambert; Daniel Mendoza-Villanueva; Rosa M Bermudez-Cruz; Patricio Gariglio Journal: Virology Date: 2013-09-27 Impact factor: 3.616
Authors: Maria Vittoria Sepporta; Francesca Maria Tumminello; Carla Flandina; Marilena Crescimanno; Marco Giammanco; Maurizio La Guardia; Danila di Majo; Gaetano Leto Journal: Target Oncol Date: 2013-03-01 Impact factor: 4.493