Presentation Type
Poster
The Role of EVI1, a TGFβ Transcriptional Corepressor, in Modulating RON Tyrosine Kinase Expression and Epithelial-Mesenchymal Transition in Ovarian Cancer
Abstract
Ovarian cancer is one of the most common gynecological malignancies in the United States, affecting over 20,000 women each year. While the molecular events leading to this disease have yet to be fully elucidated, the conversion of cells from an epithelial to mesenchymal morphology (EMT) is known to have profound impacts on their invasive/metastatic ability. EMT is believed to be regulated through several cytokine and growth factor signaling pathways such as that of transforming growth factor beta (TGFβ). SnoN/SkiL and several splice variants of EVI1 (EVI1, MDS1/EVI1, EVI1Del190-515) function as transcriptional co-repressors in this pathway which are amplified at the DNA, RNA, and protein levels (CGH, qPCR, and Western analysis) in serous epithelial ovarian carcinomas. We have also shown that EVI1 can act as a transcriptional corepressor of RON tyrosine kinase, a transmembrane receptor in epithelial cells. By modulating EVI1 splice form expression, we hypothesize that the expression pattern and splice forms of RON tyrosine kinase will be altered, leading to changes in EMT in ovarian carcinoma cell lines. Furthering our understanding of this pathway could help us to identify important molecular targets which could be implemented in the early diagnosis and treatment of patients with ovarian cancer.
Categories
Biomedical Sciences
Research Type
Thesis
Mentor Information
Dr. Meera Nanjundan
The Role of EVI1, a TGFβ Transcriptional Corepressor, in Modulating RON Tyrosine Kinase Expression and Epithelial-Mesenchymal Transition in Ovarian Cancer
Ovarian cancer is one of the most common gynecological malignancies in the United States, affecting over 20,000 women each year. While the molecular events leading to this disease have yet to be fully elucidated, the conversion of cells from an epithelial to mesenchymal morphology (EMT) is known to have profound impacts on their invasive/metastatic ability. EMT is believed to be regulated through several cytokine and growth factor signaling pathways such as that of transforming growth factor beta (TGFβ). SnoN/SkiL and several splice variants of EVI1 (EVI1, MDS1/EVI1, EVI1Del190-515) function as transcriptional co-repressors in this pathway which are amplified at the DNA, RNA, and protein levels (CGH, qPCR, and Western analysis) in serous epithelial ovarian carcinomas. We have also shown that EVI1 can act as a transcriptional corepressor of RON tyrosine kinase, a transmembrane receptor in epithelial cells. By modulating EVI1 splice form expression, we hypothesize that the expression pattern and splice forms of RON tyrosine kinase will be altered, leading to changes in EMT in ovarian carcinoma cell lines. Furthering our understanding of this pathway could help us to identify important molecular targets which could be implemented in the early diagnosis and treatment of patients with ovarian cancer.
