EGFR activation of PEA3 and FOXM1 in ovarian cancer invasion

描述（由申请人提供）：卵巢癌是美国女性癌症死亡的第五大原因。虽然卵巢癌如果在转移前被发现是可以治疗的，但只有25%被诊断患有这种疾病的女性处于早期阶段。表皮生长因子受体（Epidermal growth factor receptor， EGFR）在多种人类肿瘤中发生突变或激活，这种致癌基因的激活促进了肿瘤的增殖和侵袭。EGFR在一定程度上通过启动一系列导致基因转录的信号事件来影响这些过程。确定哪些转录因子介导卵巢癌细胞运动和侵袭的变化可能会导致新的诊断标记和潜在的治疗靶点。据推测，EGFR激活的关键转录因子通过激活前侵袭途径和增加基因组不稳定性来促进卵巢癌的转移进展。我们将确定(1)EGFR是否激活卵巢癌细胞中的转录因子PEA3和FOXM1， (2) EGFR激活这些转录因子是否导致促侵袭靶基因的诱导和侵袭潜力的增加，以及(3)在人类原发性卵巢肿瘤中，EGFR是否与PEA3或FOXM1共表达。

DESCRIPTION (provided by applicant): 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.