Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Thesis
Epidermal growth factor (EGF) and transforming growth factor (TGF[beta]1) promote EMT in primary prostate cancer cells via Ras signaling. Inhibitory effects of EGCG on EMT induced matrix metalloproteinase (MMP) activity in prostate cancer cells
Master of Science (M.S.), Drexel University
2010
DOI:
https://doi.org/10.17918/etd-3307
Abstract
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 TGF[beta]1 (E+T) can promote expression of Vimentin and matrix metalloproteinases (MMP2 and MMP9) 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, TGF[beta]1 alone induced MMP2 and MMP9 secretion, whereas, E+T was essential to induce MMP2 and MMP9 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 PC3ML2 tumor cells. In sum, our work has demonstrated that specific ligands regulate EMT and that a herbal tea extract has potential therapeutic benefit in blocking ligand dependent EMT.
Metrics
59 File views/ downloads
32 Record Views
Details
- Title
- Epidermal growth factor (EGF) and transforming growth factor (TGF[beta]1) promote EMT in primary prostate cancer cells via Ras signaling. Inhibitory effects of EGCG on EMT induced matrix metalloproteinase (MMP) activity in prostate cancer cells
- Creators
- Devika M. Varma - DU
- Contributors
- Mark E. Stearns (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 3307; 991014632448904721