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Principal Investigator
Ariel Ruiz i Altaba, Ph.D. , Department of Cell Biology, New York University School
of Medicine
Background
Sporadic basal cell carcinoma (BCC) is the most common form of malignant skin cancer
affecting over 800,000 people in the US alone. It primarily affects very fair skinned
adults. Although the incidence of death following diagnosis of BCC is not as great
as with melanomas, the cost in financial terms and in the quality of life of affected
people is great. At present BCC is diagnosed using histological parameters on biopsy
samples, a method that relies on changes in tissue morphology that must be evaluated
by eye. This method not only has inherent subjectivity, but diagnosis can only be
made at later times, when cells have altered morphologically. The development of
a method to diagnose BCC at early stages would not only aid individuals with BCC
lead more productive lives, but also could reduce health care costs.
Description of Project
Dr. Ruiz i Altaba’s laboratory has discovered that virtually all sporadic BCCs
express a protein called Gli-1. In addition, Gli-1 expression is turned on very early,
before the cancer cells display transformed phenotype. Gli-1 is a zinc finger transcription
factor that serves as a target of the Sonic hedgehog (Shh) signal transduction pathway.
Shh gene encodes a secreted growth factor, which binds to its cell surface receptor,
encoded by the patched gene. Upon Shh binding to patched, several downstream proteins
are activated, leading to the activation of Gli-1. Gli-1 can then mediate the activation
of Shh target genes, which includes Shh.
Using frog embryos as a model system, the investigators showed that misexpression
of Gli-1 led to epidermal tumors. Thus Gli-1 expression can directly be linked to
tumor induction. Dr. Ruiz i Altaba has shown that Gli-1 is expressed not only in
cells which are histologically identifiable, but also in immediate cells surrounding
the tumor, which would not be recognized as cancerous by standard dermatopathological
criteria. Thus frog embryos provide a powerful tool to evaluate the tumorgenic potential
for genes.
Applications
This model system can be exploited to rapidly investigate anti-cancer agents. A major
advantage of this system is that BCCs develop on the skin, making application of
possible agents easy and scoring of assay results readily observable. One possibility
is the development of a cream or ointment that would contain an active agent that
interferes with some aspect of Shh signaling pathway, or with Gli-1 itself. The cream,
applied to very early tumors, would prevent the progression of disease.
Gli-1 can also serve as a marker for diagnosis of BCC in the early stages of the
disease. The usefulness of a kit in a dermatologist’s office to diagnose a
cancer at early stages is self evident, since in later stages of BCC patients must
resort to surgery, often facial, which can lead to cosmetic and other skin malformations.
Patent Status
A U.S. patent application has been filed covering this novel technology.
For further information please contact
New York University
Office of Industrial Liaison
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189
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