TGF? modulated changes in VEGF expression and secretion may enhance disease progression through an autocrine mechanism, 2010

Collection:
Atlanta University and Clark Atlanta University Theses and Dissertations
Title:
TGF? modulated changes in VEGF expression and secretion may enhance disease progression through an autocrine mechanism, 2010
Creator:
Darrington, Eric Brian
Contributor to Resource:
Khan, Shafiq A.
Chaudhary, Jaideep
Ananaba, Godwin
Date of Original:
2010-12-01
Subject:
Degrees, Academic
Dissertations, Academic
Location:
United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
Medium:
dissertations
theses
Type:
Text
Format:
application/pdf
Description:
Degree Type: dissertation
Degree Name: Doctor of Philosophy (PhD)
Date of Degree: 2010
Granting Institution: Clark Atlanta University
Department/ School: School of Arts and Sciences, Biology
Prostate cancer is the most common malignancy in American males, and the second leading cause of cancer deaths. Transformed cells break free of cell cycle regulation and proliferate uncontrollably. Growth factors like TGF-? and VEGF have been linked to enhanced metastasis and tumor neovascularization in prostate cancer cells; may act through autocrine mechanisms to enhance cancer development and promote metastasis. We hypothesize that VEGF plays a potential role in the enhanced metastasis of prostate cancer independent of the well studied influences it has on neovascularization. We have studied the effects of TGF-? on VEGF expression and secretion in normal prostate epithelial cells and two metastatic prostate cancer cell lines (PC3 and DU145); and we have examined the physiological significance of VEGF on cancer cells. In this investigation, we treated HPV7 and RWPE1 prostate epithelial cells and prostate cancer cells (DU145 and PC3) with l0ng/ml of recombinant human TGF-?1,TGF-?2 and TGF-?3 under normoxic and hypoxic conditions for eight hours. We observed that while TGF-? upregulated VEGF transcription under normoxic conditions in DU145 cells, TGF-? had no effect on VEGF transcription in PC3 or normal prostate epithelial cells, Additionally, cell associated VEGF protein expression was unaffected by any of the treatments in prostate cancer cells; but was significantly down regulated in normal prostate epithelial cells treated with TGF-? isoforms under hypoxic conditions. TGF? also enhanced VEGFA secretion in normal prostate epithelial cells but this effect was only observed under hypoxic conditions in prostate cancer cells. Lastly, VEGF treatment induced erk phosphorylation and appeared to significantly enhance migration in prostate cancer cells. These results suggest that VEGF may contribute to the tumorigenic effects of TGF-? and hypoxia in cancer cells through an angiogenesis independent autocrine mechanism. of TGF-~ and hypoxia in cancer cells through an angiogenesis independent autocri
Metadata URL:
http://hdl.handle.net/20.500.12322/cau.td:2010_darrington_eric_brian
Language:
eng
Holding Institution:
Clark Atlanta University
Rights:
Rights Statement information

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