Nodal and transforming growth factor-? (TGF-?) signalings in prostate cancer cells, 2013

Collection:
Atlanta University and Clark Atlanta University Theses and Dissertations
Title:
Nodal and transforming growth factor-? (TGF-?) signalings in prostate cancer cells, 2013
Creator:
Vo, BaoHan Thi
Date of Original:
2010/2019
Subject:
Degrees, Academic
Dissertations, Academic
Location:
United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
Medium:
theses
dissertations
Type:
Text
Format:
application/pdf
Description:
TGF-? signaling pathways contain both tumor suppressor and tumor promoting activities. Nodal, a TGF-? like growth factor, functions as an embryonic morphogen that maintains the pluripotency of embryonic stem cells. We demonstrated that Nodal and its receptors are expressed in prostate epithelial stem cells (WPE) and prostate cancer cells (LNCaP, LNCaP-C8 1, and DU145). Nodal also exerts differential effects on proliferation and migration in different prostate cell lines. First, we determined the comparative effects of Nodal and TGF-? on proliferation and migration under identical experimental conditions in selected prostate cell lines. Our results demonstrated that Nodal and TGF-? exerted similar biological effects on prostate cells; both inhibited proliferation in WPE, RWPE1, and DU145 cells while neither had any effect on the proliferation of LNCaP or PC3 cells. Interestingly, Nodal and TGF-? induced migration in PC3 cells, but not in DU145 cells. TGF-? induced predominantly phosphorylation of Smad3, while Nodal induced phosphorylation of only Smad2. We also determined the expression and differential role of Ski, a co-repressor of Smad2/3, in Nodal and TGF- ? signaling in prostate cancer cells. Similar levels of Ski mRNA were found in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cells and prostate cancer tissue samples. Exogenous Nodal and TGF- ? had no effects on Ski mRNA levels. On the other hand, TGF- ? induced a rapid degradation of Ski protein mediated by the proteasomal pathway while Nodal had no effect on Ski protein. Reduced Ski levels correlated with increased basal and TGF-?-induced Smad2/3 phosphorylation. Knockdown of endogenous Ski reduced proliferation in DU145 cells and enhanced migration of PC3 cells. We conclude that high levels of Ski expression in prostate cancer cells may be responsible for repression of TGF-? and Smad3 signaling, but Ski protein levels do not influence Nodal and Smad2 signaling.
Date of award: 5/1/2013
Degree type: dissertation
Degree name: Doctor of Philosophy (PhD)
Granting institution: Clark Atlanta University
Department: School of Arts and Sciences, Biology
Advisor: Khan, Shafiq A.
Advisor: Chaudhary, Jaideep
Advisor: Odero-Marah, Valerie
Metadata URL:
http://hdl.handle.net/20.500.12322/cau.td:2013_vo_baohan_t
Holding Institution:
Atlanta University Center Robert W. Woodruff Library
Rights:
Rights Statement information

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