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Profiling Established Cell Lines as a Means to Screening Diversity

Cell lines provide a readily available source of target material for functional and molecular binding screens in drug discovery. The Cell PROFILE® program at NovaScreen® represents an effort to identify receptors and enzymes expressed in established cell lines that are relevant to important drug screening endeavors. In this report, we present data on a selected number of receptors and enzymes for four cell lines studied in this survey. The objective of this survey was not to compare one cell line with another, but to illustrate the diversity of pharmacologic targets and the untapped potential of databases for readily obtainable cell lines. The following cell lines, which are all derived from human tumors, were included in this study (with some relevant pharmacologic/pathologic targets): HT-29, derived from an adenocarcinoma of the colon (colorectal cancer); SK-N-MC, derived from a neuroepithelioma (NPY receptors, apoptosis, HIV type I infection); H-4, derived from a neuroglioma (Alzheimer's disease); and LNCaP, derived from a prostate carcinoma (androgen receptor, prostate cancer). Specific to this survey were receptor-binding assays for androgens, corticotropin-releasing factor, endothelin, GABA, NMDA, somatostatin, and alpha and beta adrenergic ligands, as well as binding sites for ion channels. A comparison of specific binding of these various sites between target tissues routinely used in our assays and established cell lines reveals a diversity of receptors heretofore not reported for the latter and represents a potential database for screening and pharmacologic research.