NIH3T3 CELLS EXPRESSING THE DELETED IN COLORECTAL-CANCER TUMOR-SUPPRESSOR GENE-PRODUCT STIMULATE NEURITE OUTGROWTH IN RAT PC12 PHEOCHROMOCYTOMA CELLS

The Deleted in Colorectal Cancer (DCC) gene is a candidate turner supp ressor gene that is predicted to encode a transmembrane polypeptide, w ith strong similarity to the neural cell adhesion molecule (N-CAM) fam ily. Previous studies have suggested that several different N-CAMs, wh en expressed in nonneuronal cell types can stimulate neurite outgrowth from PC12 rat pheochromocytoma cells. Based on the predicted structur al similarity of DCC to N-CAMs, we sought to determine whether NIH3T3 cells expressing BCC could stimulate neurite outgrowth in PC12 cells. We found that NIH3T3 cell lines expressing DCC could stimulate PC12 ce lls to extend neurites. Supernatants from DCC-transfected NIH3T3 cells did not induce neurite outgrowth above background levels, suggesting that cell-cell interaction was required. NIH3T3 cells expressing a tru ncated form of DCC, lacking the majority of the cytoplasmic domain seq uences, also failed to induce neurite outgrowth above the levels seen with control NIH3T3 cells, suggesting that the cytoplasmic domain of D CC was necessary for its neurite-promoting function. In contrast to NG F-mediated neurite outgrowth, the DCC-mediated response was inhibited by treatment with pertussis toxin or the combination of N- rand L-type calcium channel blockers, and was unaffected by the transcriptional i nhibitor cordycepin. The data suggest that the DCC protein can functio n in a fashion analogous to other N-CAMs to alter PC12 cell phenotype through intracellular pathways distinct from those Involved in NGF sig naling.