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Project Title2011-039 Novel Cancer Stem Cell Biomarkers-Applications in Development of Cancer Diagnostics and Therapeutics
Track Code2011-039
Websitehttp://otc.rutgers.edu/
Short Description

Scientists at Rutgers have identified novel biomarkers in a series of evolutionary-conserved regions within and surrounding the CD44 gene, that potentially regulate its expression in normal cells and cancer stem cells. These regulatory regions direct the expression of protein coding genes in a cell-type specific manner. Using computational comparative genomic analyses, conserved cis-regulatory DNA sequences were revealed. These were subsequently amplified and incorporated into constructs for reporter assays in various breast cancer cell lines (with different levels of CD44 expression), to determine cell-type dependent expression of CD44. By identifying conserved regions that have the ability to drive CD44 expression, this technology will aid in identifying transcription factors that play an important role in its regulation and have a potential target for future therapies. For example, using targeted gene delivery systems, these DNA sequences can be integrated in vivo within genomes of organisms of interest to direct cell/tissue-specific expression and inhibit progenitor properties of cancer stem cells.

Abstract

Stem cells are important in regenerative medicine but they are also precursors for pathological conditions such as cancer. Cancerous stem cells contribute to tumor propagation, tumor heterogeneity and retain the ability to rapidly differentiate. Unfortunately, they are also immune to many cancer therapies. CD44 is a multifunctional cell surface glycoprotein involved in cell proliferation, angiogenesis, cell migration, invasion and metastasis. It is also highly expressed in primary and metastatic cancer cells such as human breast cancer, prostate cancer and others. Scientists at Rutgers have identified novel biomarkers in a series of evolutionary-conserved regions within and surrounding the CD44 gene, that potentially regulate its expression in normal cells and cancer stem cells. These regulatory regions direct the expression of protein coding genes in a cell-type specific manner. Using computational comparative genomic analyses, conserved cis-regulatory DNA sequences were revealed. These were subsequently amplified and incorporated into constructs for reporter assays in various breast cancer cell lines (with different levels of CD44 expression), to determine cell-type dependent expression of CD44. By identifying conserved regions that have the ability to drive CD44 expression, this technology will aid in identifying transcription factors that play an important role in its regulation and have a potential target for future therapies. For example, using targeted gene delivery systems, these DNA sequences can be integrated in vivo within genomes of organisms of interest to direct cell/tissue-specific expression and inhibit progenitor properties of cancer stem cells.

 
Tagsbreast cancer, Cancer Stem Cell Biomarkers, glioblastoma, Head and Neck Squamous Cell Carcinoma, leukemia, Pancreatic Cancer., prostate cancer
 
Posted DateJun 11, 2012 10:08 AM

Researcher

Name
Li Cai

Manager

Name
Stuart Palmer

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