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Ph.D. (1996)
University of
Wisconsin
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Shuyuan Yeh
Assistant Professor
of Urology and of Pathology
and Laboratory Medicine
Primary Appointment:
Urology
GEBS Cluster
Affiliations:
PWD - Pathways of Human Disease
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Research:
1) Chemopreventive roles of vitamin E in prostate cancer,
2) the cross talk of kinase pathways, androgen receptor and
coregulators. |
Contact Information:
E-mail:
Shuyuan_Yeh@urmc.rochester.edu |
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 626
Rochester, New York 14642
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Medical Center, Room 1-5340
Phone: (585) 275-3346
Fax: (585) 756-4133 |
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Research
Overview
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1. Chemopreventive roles of vitamin E in prostate cancer:
Epidemiological evidence indicates that a daily supplement with
vitamin E derivatives could reduce the risk of prostate cancer,
however, the detailed mechanism remains unclear. We demonstrate
that vitamin E succinate (alpha-VES, RRR-alpha-tocopheryl succinate)
can suppress the expression of prostate-specific antigen (PSA),
a marker for progression of prostate cancer. VES can also suppress
the androgen receptor (AR) expression. Cell growth studies further
showed VES could inhibit the growth of prostate cancer cells.
Compared with alpha-Vit E and gamma-Vit E, our results also
suggested that the VES is a better inhibitor of prostate cnacer
cell growth. Together, our data indicated that alpha-VES might
suppress cell growth via inhibition of androgen/AR-mediated
functions, which could be a novel mechanism to elucidate how
VES inhibits the growth of prostate cancer cells. In addition
to investigating the molecular mechanism of androgen/AR, we
have found that VES may target on other intracellular molecules
to inhibit the growth of prostate cancer cells. To elucidate
the mechanism of how alpha-VES affects cancer cell growth, we
set our goals to explore the molecular mechanisms of alpha-vitamin
E in prostate cancer. Currently, we are applying cDNA array
to identify the vitamin E target genes in the prostate cancer
cells. In addition, a point mutation on the vitamin E carrier
protein has been identified in my lab. We are in the progress
to analyze the mutation in cancer tissues.
2. The cross talk of kinase pathway, androgen receptor and
coregulators:
To date, prostate cancer patients originally respond to the
androgen ablation therapy but eventually succumb to disease.
Collectively, the proposed explanations such as mutations of
AR, the change of the steroid specificity of AR through AR mutations,
or through AR interaction with coregulators, have been actively
investigated. Furthermore, the induction of AR transactivation
through the phosphorylation signal cascade may provide an alternative
explanation of why the activation of AR is less dependent on
androgens. Thus, part of our study plan focuses on kinase signal
on AR transactivation in prostate cancer, and identification
of in vivo MAP kinase target site on AR. The accomplishment
of this study would provide valuable information on how MAP
kinase signal cross talks to AR and AR associated proteins in
molecular mechanism and the pathogenesis of prostate cancer
(This work is supported by NIH grant RO1 DK60912-01, effected
peroid: 10/01- 9/05). |
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Recent Publications
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Zhang Y, Jing N, E. Chang, Messing EM, Chin-Rang
Yang and Yeh S. (2002) "alpha-Vitamin E Inhibition of AR function
and the expression of prostate specific antigen in prostate
cancer cells." (PNAS in press, 2002).
Lin HK, Yeh S, Kang HY, Chang C. Akt
suppresses androgen-induced apoptosis by phosphorylating and
inhibiting androgen receptor. Proc Natl Acad Sci U S A.
2001 Jun 19;98(13):7200-5.
Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting
HJ, Kang HY, Chang C. Increase
of androgen-induced cell death and androgen receptor transactivation
by BRCA1 in prostate cancer cells. Proc Natl Acad Sci
U S A. 2000 Oct 10;97(21):11256-61.
Yeh S, Kang HY, Miyamoto H, Nishimura K,
Chang HC, Ting HJ, Rahman M, Lin HK, Fujimoto N, Hu YC, Mizokami
A, Huang KE, Chang C. Differential
induction of androgen receptor transactivation by different
androgen receptor coactivators in human prostate cancer DU145
cells. Endocrine. 1999 Oct;11(2):195-202.
Yeh S, Lin HK, Kang HY, Thin TH, Lin MF,
Chang C. From
HER2/Neu signal cascade to androgen receptor and its coactivators:
a novel pathway by induction of androgen target genes through
MAP kinase in prostate cancer cells. Proc Natl Acad Sci
U S A. 1999 May 11;96(10):5458-63.
Yeh S, Chang HC, Miyamoto H, Takatera H,
Rahman M, Kang HY, Thin TH, Lin HK, Chang C. Differential
induction of the androgen receptor transcriptional activity
by selective androgen receptor coactivators. Keio J Med.
1999 Jun;48(2):87-92. Review.
Yeh S, Miyamoto H, Nishimura K, Kang H, Ludlow
J, Hsiao P, Wang C, Su C, Chang C. Retinoblastoma,
a tumor suppressor, is a coactivator for the androgen receptor
in human prostate cancer DU145 cells. Biochem Biophys
Res Commun. 1998 Jul 20;248(2):361-7.
Links are to the PubMed publication list.
PubMed is maintained by the National Library of Medicine and
provides abstracts of publications as well as links to the
full text of many articles (at journal homepages).
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