Upregulated INHBA Expression May Promote Cell Proliferation and is Associated with Poor Survival in Lung Adenocarcinoma

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2009 Mar 25

PMID 19308293

Citations 72

Authors

Christopher W Seder

Wibisono Hartojo

Lin Lin

Amy L Silvers

Zhuwen Wang

Dafydd G Thomas

Thomas J Giordano

Guoan Chen

Andrew C Chang

Mark B Orringer

David G Beer

Affiliations

Soon will be listed here.

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.

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