Gene expression profile in early stage of retinoic acid-induced differentiation of human SH-SY5Y neuroblastoma cells

Purpose: The human SH-SY5Y cell line is an established model for retinoic a cid (RA)-induced neural differentiation. We employed a broad human 15K micr oarray (15,000 genes) and focused Neuroarray (1152 genes) to examine change s in gene expression early in the process of differentiation (6 hr), before morphology or growth changes are observed. Methods: P-33-labeled cDNA probes prepared from RNA extracts of RA-treated and control cultures were hybridized to array membranes, and levels of expr ession were quantified and compared. Results: In the 15K array, 19 % of the genes were decreased (0.4 % were nam ed genes and the remainder were expressed sequence tags (ESTs) or unknowns) , and 9 % were increased (4.2 % named genes). In the Neuroarray, 3 % were d ecreased and 8 % were increased. Conclusions: Summary gene profiles are presented, which include transcripti on factors, genes associated with cell cycle, cell shape, neurotransmission , intermediary filaments, and others. The prevalence of down-regulated gene s in the broad 15K array and up-regulated genes in the neuro-focused array suggests a pattern shift in gene expression associated with differentiation . The predominance of ESTs among the down-regulated genes indicates a great number of as-yet-unidentified genes are repressed in early stage neural di fferentiation.