cDNA cloning and mapping of mouse pleckstrin (Plek), a gene upregulated intransformation-resistant cells

Changes that occur during tumor promotion, the rate-limiting phase of multi step carcinogenesis, may offer the best targets for prevention of cancer or reversal of early disease. The murine epidermal JB6 promotion-sensitive (P +) and -resistant (P-) cell lines provide a cell culture model for tumor pr omoter-induced neoplastic transformation ideally suited to the identificati on of molecular events that mediate or inhibit transformation. A differenti al display comparison of P+ and P- cell mRNAs yielded seven differentially expressed sequences. One of the sequences preferentially expressed in P- ce lls identified an similar to 3.6-kb message that was induced to higher leve ls in P- cells following exposure to the tumor promoter 12-O-tetradecanoylp horbol acetate than in P+ cells. The message was detected in mRNA from hear t, lung, and spleen. cDNA cloning of the P- preferential sequence revealed a high degree of identity to human pleckstrin (PLEK), the major PKC substra te in platelets (Tyers et al., 1988, Nature 333: 470). We report the comple te mouse cDNA sequence of pleckstrin and the localization of the gene to ch romosome 11, its expression in a nonhematopoetic cell line, and its potenti al role in blocking neoplastic transformation.