Microarray analysis of gene expression in proliferating Schwann cells: synergistic response of a specific subset of genes to the mitogenic action of heregulin plus forskolin.

Cultured Schwann cells treated with heregulin growth factor require costimulation with a cyclic adenosine monophosphate-elevating agent to produce maximal cell proliferation. Gene chip expression analysis was used to identify genes that are induced or repressed when Schwann cells are treated with heregulin and/or forskolin. By utilizing arrays that contained 8799 probes, the expression of over 1000 genes was found to be significantly changed after 30 hr of treatment with heregulin, forskolin, or heregulin plus forskolin. Hierarchical clustering revealed groups of genes with distinct expression patterns. Of particular interest was a cluster of 140 genes that were up-regulated by heregulin plus forskolin but not by heregulin or forskolin alone. Many of the genes in this group have roles in cell division, such as cyclin B, cyclin D3, E2F-5, cdc 25B, polo-like kinase, and protein kinase C type III. These findings identify a profile of gene expression for Schwann cell proliferation. Copyright 2003 Wiley-Liss, Inc.