Sung-Jen Wei, PhD
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Sung-Jen Wei, PhD
Deaprtment of Pharmacology
Medical Research Division
Edinburg Regional Academic Health Center (E-RAHC)
1214 West Schunior Street
Edinburg, TX 78541
cancer has become a worldwide public health problem, with nearly one
million new cases of skin cancers yearly in the United States. It is
well known that skin cancers including non-melanomas and melanomas
are, most likely, the result of complex interactions between host risk
factors (genetic aberrations and immunosuppression) and environmental
exposures to ultraviolet irradiation and chemical carcinogens. The
non-melanoma skin cancers, including basal cell carcinoma (BCC) and
squamous cell carcinoma (SCC), account for approximately 80% and 16%
of all skin cancers, respectively, whereas malignant melanomas account
for only 4% of all skin cancers. BCC and SCC are both derived from the
basal layer of the epidermis of the skin. BCC grows slowly and rarely
metastasizes, whereas SCC is highly invasive and metastasized
frequently. The majority of skin cancer related deaths are due to the
metastasis. Through better understanding of molecular mechanisms
underlying human skin carcinogenesis, we will be able to develop
effective tools, such as specific gene chip and powerful drugs, to
develop targeted molecular diagnosis and therapeutics in the clinic.
Much of our knowledge of multistage skin carcinogenesis, defined by
initiation, promotion and progression to malignancy, is derived from
the studies of mouse models, which have shown aberrations in oncogenes
and tumor suppressor genes during neoplastic development. The
molecular changes associated with the early stages of skin tumor
formation have yet to be determined. The goals of our studies are to
identify novel genes involved in early skin neoplastic development
using a Tg.AC transgenic mouse model. This model possesses a v-Ha-ras
transgene under the regulation of a fetal zeta-globin gene promotor
which confers a unique phenotype of inducible skin papillomas with a
high rate of progression to highly invasive squamous and spindle cell
neoplasms. A body of evidence supports that keratinocyte stem cells (KSCs)
residing in the hair follicle bulge region have long been thought to
be a major carcinogen target which give rise to the latent neoplastic
pool that clonally expand into cutaneous tumors. The candidate KSC
population was isolated using fluorescence-activated cell sorting (FACS)
from Tg.AC mice hyperplastic skin, which has been treated with a tumor
promoter called 12-O-tetradecanoylphorbol-13-acetate (TPA), and their
gene expression was analyzed using a mouse cDNA microarray technology.
Interestingly, we have identified 11 genes whose expression changed
significantly in the population of TPA-treated KSCs. Two up-regulated
genes, DSS1 and nm-23/NDPK-B, have been identified and characterized
as critical TPA-inducible genes expressed in KSCs, with possible
involvement in early skin carcinogenesis.
More recently, our laboratory is also interested in identifying a role
of the Deleted in Split hand/Split foot gene 1 (DSS1) in cancers. Our
data indicates that DSS1 might play a critical role in regulating
protein degradation functions through the ubiquitin-proteasome system
(UPS). DSS1 is a gene associated with a human inherited heterogeneous
limb developmental disorder called split hand/split foot malformation
type 1 (SHFM1). This discovery is important since proteasome, besides
being involved in basic biological processes leading to specific
protein degradation and specific cellular pathway, has been implicated
as playing a role in human disease states. Currently one proteasome
specific inhibitor (Bortezomib or Velcade) has been developed by the
Millennium pharmaceutical company and is in clinical use to treat
patients with relapse multiple myeloma. The DSS1/proteasome
interaction may provide an alternative mechanism to specifically
inhibit proteasomal activity. It is anticipated that further
exploitation of the DSS1/proteasome interaction could lead to the
development of a new drug with important clinical potential for
cancers, heart diseases, aging related and neurodegenerative
1. Identification of a specific motif of the DSS1 protein required for
proteasome interaction and p53 protein degradation. Sung-Jen Wei,
Jason Williams, Hong Dang, Thomas A. Darden, Bryan L. Betz, Margaret
M. Humble, Fang-Mei Chang, Carol S. Trempus, Katina Johnson, Ronald E.
Cannon, and Raymond W. Tennant. Journal of Molecular Biology, 383:
2. Comprehensive microarray transcriptome profiling of CD34-enriched
mouse keratinocyte stem cells. Trempus, CS, Dang H, Humble MM, Wei SJ,
Gerdes M, Morris RJ, Bortner CD, Cotsarelis G, and Tennant RW. Journal
of Investigative Dermatology, 127: 2904-2907, 2007.
3. Identification of genes and gene ontology processes critical to
skin papilloma development in Tg.AC transgenic mice. Hong Dang, Carol
S. Trempus, David E. Malarkey, Sung-Jen Wei, Margaret M. Humble,
Rebecca J. Morris, and Raymond W. Tennant. Molecular Carcinogenesis,
45: 126-140, 2006.
4. The Ins (1, 3, 4) P 3 5/6-kinase/Ins (3, 4, 5, 6) P 4 1-kinase is
not a protein kinase. Qian X, Mitchell J, Wei SJ, Williams J,
Petrovich RM, Shears SB. Biochemical Journal, 389: 389-395, 2005.
5. 12-O-tetradecanoylphorbol-13-acetate and UV radiation-induced
nucleoside diphosphate protein kinase B mediates neoplastic
transformation of epidermal cells. Sung-Jen Wei, Carol S. Trempus,
Robin C. Ali, Laura A. Hansen, and Raymond W. Tennant. Journal of
Biological Chemistry, 279:5993-6004, 2004.
6. IFN-beta induces caspase-mediated apoptosis by disrupting
mitochondria in human advanced stage colon cancer cell lines. Juang SH,
Wei SJ, Hung YM, Hsu CY, Yang DM, Liu KJ, Chen WS, Yang WK. Journal of
Interferon and Cytokine Research, 24: 231-243, 2004.
7. Colon cancer cells with high invasive potential are susceptible to
induction of apoptosis by a selective COX-2 inhibitor. Chen WS, Liu JH,
Wei SJ, Liu JM, Hong CY, Yang WK. Cancer Sciences, 94: 253-258, 2003.
8. Identification of Dss1 as a
12-O-tetradecanoylphorbol-13-acetate-responsive gene expressed in
keratinocyte progenitor cells, with possible involvement in early skin
tumorigenesis. Sung-Jen Wei, Carol S. Trempus, Ronald E. Cannon, Carl
D. Botner, and Raymond W. Tennant. Journal of Biological Chemistry,
278: 1758-1768, 2003.
9. Combination gene therapy of cancer: granulocyte-macrophage colony
stimulating factor enhances tumor regression induced by herpes simplex
virus thymidine kinase/ganciclovir “suicidal” treatment in a mouse
tumor model. Wei SJ, Yang WK, Ch’ang LY, Yang DM, Hung YM, Lin WC.
Journal of Genetics and Molecular Biology, 13: 194-208, 2002.
10. Tumor invasiveness and liver metastasis of colon cancer cells
correlated with cyclooxygenase-2 expression and inhibited by a
COX-2-selective inhibitor, etodolac. Chen WS, Wei SJ, Liu JM, Hsiao M,
Lin JK, Yang WK. International Journal of Cancer, 91: 894-899, 2001.
11. PIK3CA as an oncogene in cervical cancer. Wei SJ, Ma YY, Lin YC,
Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY.
Oncogene, 19: 2739-2744, 2000.
12. Involvement of Fas (CD95/APO-1) and Fas ligand in apoptosis
induced by ganciclovir treatment of tumor cells transduced with herpes
simplex virus thymidine kinase. S-J Wei, Y Chao, Y-L Shih, D-M Yang,
Y-M Hung, and W K. Yang. Gene Therapy, 6: 420-431, 1999.
13. S- and G2-phase cell cycle arrests and apoptosis induced by
ganciclovir in murine melanoma cells transduced with herpes simplex
virus thymidine kinase. Sung-Jen Wei, Yee Chao, Yi-Mei Hung, Wen-chang
Lin, Den-Mei Yang, Yung-Luen Shih, Lan-Yang Ch’ang, Jacqueline
Whang-Peng, and Wen K. Yang. Experimental Cell Research, 241: 66-75,
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