ADRM1-amplified metastasis gene in gastric cancer

Marlena S. Fejzo, Lee Anderson, Hsiao Wang Chen, Adrian Anghel, Jiaying Zhuo, Ravi Anchoori, Richard Roden, Dennis J. Slamon

Research output: Contribution to journalArticle

Abstract

The proteasome ubiquitin receptor ADRM1 has been shown to be a driver for 20q13.3 amplification in epithelial cancers including ovarian and colon cancer. We performed array-CGH on 16 gastric cancer cell lines and found 20q13.3 to be amplified in 19% with the minimal amplified region in gastric cancer cell line AGS spanning a 1 Mb region including ADRM1. Expression microarray analysis shows overexpression of only two genes in the minimal region, ADRM1 and OSBPL2. While RNAi knockdown of both ADRM1 and OSBPL2 led to a slight reduction in growth, only ADRM1 RNAi knockdown led to a significant reduction in migration and growth in soft-agar. Treatment of AGS cells with the ADRM1 inhibitor RA190 resulted in proteasome inhibition, but RNAi knockdown of ADRM1 did not. However, RNAi knockdown of ADRM1 led to a significant reduction in specific proteins including MNAT1, HRS, and EGFR. We hypothesize that ADRM1 may act in ADRM1-amplified gastric cancer to alter protein levels of specific oncogenes resulting in an increase in metastatic potential. Selective inhibition of ADRM1 independent of proteasome inhibition may result in a targeted therapy for ADRM1-amplified gastric cancer. In vivo models are now warranted to validate these findings.

Original languageEnglish (US)
Pages (from-to)506-515
Number of pages10
JournalGenes Chromosomes and Cancer
Volume54
Issue number8
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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  • Cite this

    Fejzo, M. S., Anderson, L., Chen, H. W., Anghel, A., Zhuo, J., Anchoori, R., Roden, R., & Slamon, D. J. (2015). ADRM1-amplified metastasis gene in gastric cancer. Genes Chromosomes and Cancer, 54(8), 506-515. https://doi.org/10.1002/gcc.22262