Ovarian cancer is the fifth leading cause of death from cancer in women in the United States. Although ovarian cancer is treatable if detected before it metastasizes, only 25 percent of women diagnosed with this disease are in the early stages. Epidermal growth factor receptor (EGFR) is mutated or activated in a wide range of human tumors and activation of this oncogene promotes increased proliferation and invasion. EGFR influences these processes in part by initiating a series of signaling events that lead to gene transcription. Identifying which transcription factors mediate changes in ovarian cancer cell motility and invasion may lead to novel diagnostic markers and potential therapeutic targets. It is hypothesized that EGFR activation of key transcription factors contributes to metastatic progression in ovarian cancer through activation of pro-invasive pathways and increasing genomic instability. It will be determined (1) if EGFR activates the transcription factors PEA3 and FOXM1 in ovarian cancer cells, (2) if EGFR activation of these transcription factors results in induction of pro-invasive target genes and increased invasive potential, and (3) if in human primary ovarian tumors EGFR is co-expressed with either PEA3 or FOXM1. ? ? ?
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| Cowden Dahl, Karen D; Symowicz, Jaime; Ning, Yan et al. (2008) Matrix metalloproteinase 9 is a mediator of epidermal growth factor-dependent e-cadherin loss in ovarian carcinoma cells. Cancer Res 68:4606-13 |
| Cowden Dahl, Karen D; Zeineldin, Reema; Hudson, Laurie G (2007) PEA3 is necessary for optimal epidermal growth factor receptor-stimulated matrix metalloproteinase expression and invasion of ovarian tumor cells. Mol Cancer Res 5:413-21 |
