Abstract 1534: Identification of LMX1B as a novel oncogene in human ovarian cancer

Abstract

Abstract Ovarian cancers are thought to result from the accumulation of multiple genetic aberrations that transform ovarian and/or fallopian tube surface epithelial cells, allowing for their abnormal growth, proliferation and metastasis. We carried out genome-wide copy-number analysis using array comparative genomic hybridization on a panel of mouse ovarian cancer (OVCA) cell lines previously established in our laboratory. We identified a recurrent focal amplification on mouse chromosomal region 2qB, which contains the LIM homeodomain containing transcription factor 1B (Lmx1b) gene. LMX1B is not expressed in normal human ovary, but is expressed in many human OVCA cell lines and primary tumors. High expression of LMX1B correlates with poor outcome. To clarify the role of LMX1B in ovarian carcinogenesis, we transduced LMX1B into a panel of mouse and human OVCA cell lines and demonstrated that LMX1B strongly promotes migration of cancer cells in culture and accelerates xenograft growth in nude mice. Conversely, knockdown of LMX1B in a human cell line with endogenous high expression of LMX1B inhibits cell migration in vitro and tumor growth in vivo. Microarray analysis of cells overexpressing LMX1B identified NF-κB pathway as a potential mediator of tumor progression and subsequent treatment of NF-κB inhibitor decreased the migratory capacity of these cells. Thus, our data demonstrate that LMX1B functions as an oncogene in OVCA pathogenesis. Citation Format: Gayatry Mohapatra, Lei He, Lankai Guo, Vinod Vathipadiekal, Petra Sergent, Whitfield Growdon, Bo Rueda, David Engler, Sandra Orsulic, Michael Birrer. Identification of LMX1B as a novel oncogene in human ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1534. doi:10.1158/1538-7445.AM2014-1534