Project Details
Abstract
Head and neck cancer (HNC) is the sixth most frequent cancer in the world with an estimated
over 500,000 new cases being diagnosed annually. In Taiwan, the incidence of head and neck cancer
has become the 7th leading cancer, the 5th leading cancer in male, and is still increasing in the recent
years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it
has tremendous impact of family and society. For treatment, although local control and survival rates
are acceptable for early staged tumor, in advanced tumor, bulk tumor or lymph node metastasis, that
is, the highly invasive characteristic of the tumor is the common cause of treatment failure. Therefore,
this malignant disease cannot be controlled, unless the better understanding of the molecular
pathology in cancer growth and invasion as well as the advances of therapeutic techniques can been
developed.
Through differential display technique, we have previously identified several head and neck
cancer-associated genes, including DSG3, which is over-expressed in the cancer tissues. DSG3 is a
member of desmoglein family, belonging to the cadherin family of Ca(+2)-dependent cell adhesion
molecules. We therefore hypothesize that over-expression of DSG3 is involved in the invasiveness
and aggressiveness of head neck cancer, and that DSG3 is a potential target for molecular therapy of
head neck cancer. The main objectives of this proposal are to investigate and clarify the functional
role of DSG3 in the head and neck cancer, and investigate the potential application of modulating this
molecular in cancer treatment. The following specific aims will be accomplished to unveil such
questions.
Specific Aim #1: Study in cellular level. Examination of the cellular effects of DSG3 after alteration
of the DSG3 expression in cells. (1) Construction of the RNA interference plasmid and transfection of
the gene into head neck cancer cells. (2) Study the effects of DSG3-RNAi in cellular homeostatsis,
including cell growth/viability, colony formation, cell cycle distribution, cell migration and invasion
ability.
Specific Aim #2: Study in biochemical level. Investigation of the DSG3 signal pathway in cancer
cells. (1) Examining the possible alteration of the potential down-stream signal targets of DSG3
molecules: β-catenin and plakoglobin after modulation of DSG3 by RNAi. (2) Examining the possible
alteration of plakoglobin target in Tcf/Lef promoter genes (Tcf/Lef. c-myc, cyclin D1) leading to cell
proliferation by luciferase reporter and western blot analysis.
Specific Aim #3: Study in animal level. (1) Examining the effects of tumor growth and survival after
DSG3-RNAi delivery into subcutaneous (for growth evaluation) or intravenous (for invasion evaluation)
injected xenograft tumor mice using subcutaneous (for growth evaluation) or intravenous (for invasion
evaluation) injection technique. (2) Examining the DSG3 expression in the tumor sections by
immunohistochemistry. (3) Examining the histological apoptotic status.
Specific Aim #4: Study in clinical level. Evaluation of DSG3 protein levels in the normal and cancer
tissues. (2) Correlation of DSG3 expression with the cliniclpathological features and treatment
outcome.
Project IDs
Project ID:PC9706-0154
External Project ID:NSC95-2320-B182-024-MY3
External Project ID:NSC95-2320-B182-024-MY3
Status | Finished |
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Effective start/end date | 01/08/08 → 31/07/09 |
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