Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 25,000 ovarian cancers are diagnosed in the United States annually, and 75% of cases are in the advanced stage when they are largely incurable. There is a critical need for improved early detection tools and development of novel treatments. Recently, we showed that among 20q13-amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification and was significantly upregulated with respect to stage, recurrence, and metastasis. In addition, overexpression of ADRM1 correlated significantly with shorter time to recurrence and overall survival. Herein, array-CGH and microarray expression of ovarian cancer cell lines provides evidence consistent with the primary tumor data that ADRM1 is a 20q13 amplification target. Knockdown of ADRM1 in amplified ovarian cell-line OAW42 results in downregulation of growth factor GIPC1 and upregulation of tumor-suppressor RECK RNA and protein. In our dataset of 141 ovarian primary tumors, ADRM1 overexpression significantly correlates with GIPC1 overexpression. In addition, there is a significant anticorrelation between ADRM1 overexpression and RECK expression. Further research is necessary to determine whether targeting knockdown of ADRM1 in 20q13-amplified ovarian cancers results in growth inhibition and tumor suppression via downstream targets GIPC1 and RECK.
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PMID:Knockdown of ovarian cancer amplification target ADRM1 leads to downregulation of GIPC1 and upregulation of RECK. 2143 40

Approximately 25,000 ovarian cancers are diagnosed in the U.S. annually, and 75% are in the advanced stage and largely incurable. There is critical need for early detection tools and novel treatments. Proteasomal ubiquitin receptor ADRM1 is a protein that is encoded by the ADRM1 gene. Recently, we showed that among 20q13-amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification and was significantly upregulated with respect to stage, recurrence, and metastasis. Its overexpression correlated significantly with shorter time to recurrence and overall survival. Array-CGH and microarray expression of ovarian cancer cell lines provided evidence consistent with primary tumor data that ADRM1 is a 20q13 amplification target. Herein, we confirm the ADRM1 amplicon in a second ovarian cancer cohort and define a minimally amplified region of 262 KB encompassing seven genes. Additionally, using RNAi knock-down of ADRM1 in naturally amplified cell line OAW42 and overexpression of ADRM1 via transfection in ES2, we show that (1) ADRM1 overexpression increases proliferation, migration, and growth in soft agar, and (2) knock-down of ADRM1 results in apoptosis. Proteomic analysis of cells with ADRM1 knock-down reveals dysregulation of proteins including CDK-activating kinase assembly factor MAT1. Taken together, the results indicate that amplified ADRM1 is involved in cell proliferation, migration and survival in ovarian cancer cells, supporting a role as an oncogene and novel therapeutic target for ovarian cancer.
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PMID:Amplification Target ADRM1: Role as an Oncogene and Therapeutic Target for Ovarian Cancer. 2337 18