title: Knockdown of ovarian cancer amplification target ADRM1 leads to downregulation of GIPC1 and upregulation of RECK.
abstract: 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.
authors: Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA. mfejzo@mednet.ucla.edu
authors: Marlena S
authors: MS
authors: Fejzo
authors: Chuck
authors: C
authors: Ginther
authors: Judy
authors: J
authors: Dering
authors: Lee
authors: L
authors: Anderson
authors: Natarajan
authors: N
authors: Venkatesan
authors: Gottfried
authors: G
authors: Konecny
authors: Beth
authors: B
authors: Karlan
authors: Dennis J
authors: DJ
authors: Slamon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C500781:ADRM1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C492009:GIPC1 protein, human; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human