Modulation of NCAM expression by transforming growth factor-beta, serum, and autocrine factors

The expression of NCAM (neural cell adhesion molecule) is precisely regulated in terms of cell type specificity and developmental control. We searched for extracellular factors that may be involved in this regulation using N2A neuroblastoma and NIH 3T3 fibroblastic cells. Factors contained in FBS promoted a two- to threefold increase in NCAM protein and mRNA abundance in both cell lines. This increase in NCAM expression in high serum could be entirely attributed to enhanced levels of the NCAM-140 message. Modulation of NCAM synthesis via an autocrine mechanism is suggested by the observation that medium conditioned by N2A cells stimulated NCAM mRNA expression by 3T3 and N2A cells. Among the pure factors tested, transforming growth factor-beta (TGF beta) was found to act as an inducer of NCAM expression in 3T3 but not in N2A cells. 3T3 cells responded to exposure to TGF beta with a two- to threefold increase in NCAM protein and mRNA. Exposure of early- passage embryonic cells to TGF beta resulted in four- and twofold increases in NCAM protein and mRNA abundance, respectively, suggesting a role for TGF beta in modulating NCAM expression in the embryo. TGF beta seems to act by stimulating the transcriptional activity of the NCAM gene because it did not affect transcript stability and stimulated transcription from a proximal promoter element of the NCAM gene.