Molecular Mechanisms of Drugs Using cDNA Microarrays

Basic Sciences

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Abstract

Another area, which we will focus on, is the monitoring of gene expression changes impacted by drugs. The choice and design of many chemotherapeutic agents currently used in cancer treatment has been traditionally empirical in nature. The molecular mechanisms of their actions are not well understood, and their mode of action is often indiscriminate targeting, both of tumor and normal cells. As a model system, we have investigated the gene expression alterations during neural differentiation of the neuroblastoma (NB) cell line SMS-KCNR by retinoic acid (RA) as well as Fenretinide (4-HPR) using cDNA microarrays. Neuroblastoma is the most frequently occurring extracranial solid tumor of childhood and has the highest rate of spontaneous regression of any human cancer. RA is known to stimulate morphological neural differentiation of NB. It has been shown to enhance neurite extension, increase membrane excitability, induce neurotransmitter enzymes, and reduce tumorogenicity, as well as improve prognosis for high-stage disease. Neuroblastoma will be treated with all-trans retinoic acid (ATRA), or 4-HPR or the solvent ethanol (control) and gene expression profiles will be performed at different time points. By this method we will identify pathways of critical genes involved in neuronal differentiation and apoptosis.