Gene Analysis Links Transporter Protein to Alzheimer's Disease

Researchers have used amplified differential gene expression (ADGE) and ADGE microarray technology to examine cell lines made to express high levels of human ABCA2 transporter protein. Human ABCA2 transporter is a member of a large family of ATP-binding proteins that transport a variety of macromolecules across biologic membranes and, more specifically, its overexpression has been implicated in the acquired resistance of cells to the chemotherapeutic drug estramustine.

Investigators at Fox Chase Cancer Center (Philadelphia, PA, USA) designed ADGE to quadratically magnify the ratios of genes in two samples with the integration of DNA reassociation and polymerase chain reaction (PCR). Quadratic magnification and PCR amplification of templates improve the sensitivity and accuracy of gene expression profiling. ADGE microarray combines the high throughput of microarray and the sensitivity and accuracy of ADGE. Compared to regular microarray, ADGE microarray improves the sensitivity and accuracy of gene expression profiling, enhances the signal intensities, and requires less starting material.
Using these methods to study a line of cells genetically engineered to overexpress the gene for ABCA2, the investigators reported in the May 20, 2004, online edition of the Federation of American Societies for Experimental Biology Journal that the ABCA2 transfected cell line expressed resistance to a free radical initiator. This finding confirmed the involvement of this protein in protection against reactive oxygen species and suggested a possible link to Alzheimer's disease.
"The overexpression of the ABCA2 protein has been implicated in acquired resistance of tumors to the drug estramustine, which is used to treat prostate cancer patients,” explained senior author Dr. Kenneth D. Tew, now chairman of the department of cell and molecular pharmacology and experimental therapeutics at the Medical University of South Carolina (Charleston, USA). "This transporter is also expressed at high levels in brain tissue and may be linked with the transport of molecules relevant to the etiology of Alzheimer's disease, including those involved in the formation of amyloid plaques.

The association of the transporter with Alzheimer's first emerged from a comparative gene expression pattern analysis that we did. In samples of brain sections from Alzheimer's patients, the ABCA2 protein shows unusual patterns. That also suggests that this transporter has a possible role in Alzheimer's.”
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