ADRM1‐amplified metastasis gene in gastric cancer. Issue 8 (6th June 2015)

• Record Type: Journal Article
• Authors: Fejzo, Marlena S.; Anderson, Lee; Chen, Hsiao‐Wang; Anghel, Adrian; Zhuo, Jiaying; Anchoori, Ravi; Roden, Richard; Slamon, Dennis J.
• Is Part Of: Genes, chromosomes & cancer. Volume 54:Issue 8(2015:Aug.)
• Page Start: 506
• Page End: 515
• Publication Date: 2015-06-06
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22262
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The proteasome ubiquitin receptor <italic>ADRM1</italic> 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 <italic>ADRM1</italic>. Expression microarray analysis shows overexpression of only two genes in the minimal region, <italic>ADRM1</italic> and <italic>OSBPL2</italic>. While RNAi knockdown of both <italic>ADRM1</italic> and <italic>OSBPL2</italic> led to a slight reduction in growth, only <italic>ADRM1</italic> RNAi knockdown led to a significant reduction in migration and growth in soft‐agar. Treatment of AGS cells with the <italic>ADRM1</italic> inhibitor RA190 resulted in proteasome inhibition, but RNAi knockdown of <italic>ADRM1</italic> did not. However, RNAi knockdown of <italic>ADRM1</italic> led to a significant reduction in specific proteins including MNAT1, HRS, and EGFR. We hypothesize that ADRM1 may act in <italic>ADRM1</italic>‐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 <italic>ADRM1</italic>‐amplified gastric cancer. In vivo models are now warranted to validate these findings. © 2015 Wiley Periodicals, Inc.</p> </abstract>