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Neoplasia. 2009 Apr;11(4):388-96.

Upregulated INHBA expression may promote cell proliferation and is associated with poor survival in lung adenocarcinoma.

Author information

1
Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

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.

PMID:
19308293
PMCID:
PMC2657883
DOI:
10.1593/neo.81582
[Indexed for MEDLINE]
Free PMC Article

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