title: ADRM1-amplified metastasis gene in gastric cancer.
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. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095.
authors.forename: Marlena S
authors.initials: MS
authors.lastname: Fejzo
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095.
authors.forename: Lee
authors.initials: L
authors.lastname: Anderson
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095.
authors.forename: Hsiao-Wang
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095.
authors.forename: Adrian
authors.initials: A
authors.lastname: Anghel
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhuo
authors.affiliation: Department of Oncology, the Johns Hopkins University, Baltimore, MD, 21231.
authors.forename: Ravi
authors.initials: R
authors.lastname: Anchoori
authors.affiliation: Department of Oncology, the Johns Hopkins University, Baltimore, MD, 21231.|Department of Pathology, the Johns Hopkins University, Baltimore, MD, 21231.|Department of Gynecology and Obstetrics, the Johns Hopkins University, Baltimore, MD, 21231.
authors.forename: Richard
authors.initials: R
authors.lastname: Roden
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon