Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas

Yasushi Matsuyama, Motoshi Suzuki, Chinatsu Arima, Qin Miao Huang, Shuta Tomida, Toshiyuki Takeuchi, Ryoji Sugiyama, Yasutomo Itoh, Yasushi Yatabe, Hidemi Goto, Takashi Takahashi

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24 Citations (Scopus)

Abstract

We previously identified PSMD2, a subunit of the 19S regulatory complex of proteasomes, as a constituent of a signature associated with the acquisition of metastatic phenotype and poor prognosis in lung cancers. In the present study, we found that knockdown of PSMD2 decreased proteasome activity, and induced growth inhibition and apoptosis in lung cancer cell lines. These effects of siRNA-mediated PSMD2 inhibition were associated with changes in the balance between phosphorylated AKT and p38, as well as with induction of p21. In addition, patients with higher PSMD2 expression had poorer prognosis and a small fraction of lung cancer specimens carried increased copies of PSMD2. Notably, our findings clearly illustrate that lung adenocarcinomas can be divided into two groups; those with and without general upregulation of proteasome pathway genes including PSMD2. This general upregulation was significantly more prevalent in the non-terminal respiratory unit (non-TRU)-type, a recently proposed genetically and clinicopathologically relevant expression profile-defined classification of adenocarcinomas (P

Original languageEnglish
Pages (from-to)301-309
Number of pages9
JournalMolecular Carcinogenesis
Volume50
Issue number4
DOIs
Publication statusPublished - Apr 2011
Externally publishedYes

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Keywords

  • Apoptosis
  • Gene expression profile
  • Lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Matsuyama, Y., Suzuki, M., Arima, C., Huang, Q. M., Tomida, S., Takeuchi, T., Sugiyama, R., Itoh, Y., Yatabe, Y., Goto, H., & Takahashi, T. (2011). Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas. Molecular Carcinogenesis, 50(4), 301-309. https://doi.org/10.1002/mc.20632