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Perlecan regulation of sonic hedgehog signaling: from drosophila to humans

Prostate cancer is the second leading cause of death from cancer in men in the United
States. Most men will die of the advanced, metastatic form of the disease. Thus,
treatment strategies targeting the metastatic form of the disease are especially needed.
Emerging research on metastatic cancer highlights the importance of the
microenvironment in cancer progression and metastasis, with an emphasis on
deregulated developmental signaling in cancer progression. Research in model
organisms has shown that developmental signaling pathways are regulated by various
components of the extracellular matrix, including heparan sulfate proteoglycans. In the
model system Drosophila, the heparan sulfate proteoglycan Trol is needed for Hhdependent
proliferation in quiescent neural stem cells. In collaboration with others, I
have shown that the human homolog of Trol, PERLECAN, regulates SONIC
HEDGEHOG-dependent proliferation in advanced prostate cancer by two different
mechanisms. This makes PERLECAN a potential drug target and biomarker for prostate
cancer screening and treatment. My results also validate the discoveries made in
Drosophila in the context of human disease. With this validation, I propose and describe
the Drosophila Ejaculatory Bulb (EjB) as model for prostate cancer and prostate aging.

Identiferoai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2654
Date15 May 2009
CreatorsHernandez, Ana Maria
ContributorsDatta, Sumana
Source SetsTexas A and M University
Languageen_US
Detected LanguageEnglish
TypeBook, Thesis, Electronic Dissertation, text
Formatelectronic, application/pdf, born digital

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