Master's Thesis Defense - Epidermal Growth Factor (EGF) and Transforming Growth Factor (TGFβ1) Promotes EMT in Primary Prostate Cancer Cells via Ras Signaling
Date: June 22, 2010
Time: 9:00 AM
Location: New College Building, Room: 6101
Advisors: Peter Lelkes, Ph.D., Anat Katsir, Ph.D., and Mark Stearns, Ph.D.
Epidermal Growth Factor (EGF) and Transforming Growth Factor (TGFβ1) Promotes EMT in Primary Prostate Cancer Cells via Ras Signaling. Inhibitory Effects of EGCG on EMT Induced Matrix Metalloproteinase (MMP) Activity in Prostate Cancer Cells.
Epithelial to mesenchymal transition (EMT) may be a critical step in prostate cancer progression and metastasis. However, we do not understand the ligands and conditions controlling EMT. We have examined the factors controlling EMT in primary prostate cell lines isolated from human prostate cancer (i.e. IBC-10a and PCa-20a cells). We have shown that a combination of EGF and TGFβ1 (E+T) can promote expression of vimentin and matrix metalloproteinases (MMP-2/9) during induction of EMT in the primary cell lines. We have found that an intact Ras signaling was essential for E+T induced EMT. We have stably transfected IBC-10a cells with pBABE.ras constructs containing three distinct ras mutations (i.e., C40, G37 and S35). In cells transfected with C40 and S35, TGFβ1 alone induced MMP-2/9 secretion, whereas, E+T was essential to induce MMP-2/9 secretion in G37 transfected cells (i.e., which activates RalGDS and blocks Akt-1 and MEK signaling). Taken together, the data have shown, for the first time, that E+T activation of Akt-1 and MEK signaling pathways play a key role in EMT. One added goal of the study was to identify potential therapeutic agents which can block EMT. We have found that the green tea extract, Epigallocatechin-3-gallate (EGCG), blocks E+T induced MMP secretion in a dosage dependent manner in both the primary cell lines and malignant PC-3ML tumor cells. In sum, our work has demonstrated that specific ligands regulate EMT and that an herbal tea extract has potential therapeutic benefit in blocking ligand dependent EMT.
The New College Building is located at 245 N. 15th Street (15th & Race), and can be reached from main campus via the Dragon Route shuttle that boards at 33rd and Market.