We have investigated the expression of the c-raf-1 proto-oncogene in neoplastic and hyperplastic pathologies, as well as in normal tissues. All small cell lung carcinomas examined express elevated levels of raf transcript. Characterization of surface markers revealed the presence of early monomyelocyte antigens on cultured SCLC cell lines as well as on cells obtained from fresh biopsies. The expression of these and other surface workers is altered following treatment with gamma interferon; surprisingly, some cells began expressing T-cell markers following treatment. Employing an anti-peptide antiserum directed toward v-raf/c-raf shared determinants, the distribution of raf in normal rat brain was examined. Specific binding was observed which in some areas represented fiber tracts, while in other areas neuron bodies were strained. The distribution seen corresponds to specific cytoarchitectural sites: ventral thalamus, hippocampus, caudate putamen, septum, entorhinal cortex, inferior colliculus, and cerebellar nuclei. Regions representing the limbic system are especially enriched for the raf polypeptide. The pattern is that of a widely disseminated neuropeptide receptor. Two neural crest-derived malignancies (Ewing's sarcomas and neuroepitheliomas) have been found which express raf while neuroblastomas express significant amounts of raf RNA and protein only following cAMP induced differentiation. We have constructed two vectors containing either the complete raf cDNA sequence or the anticomplementary 3' domain obtained from the preceding sequence for the purpose of 1) identifying raf's endogenous ligand and 2) ascertaining its role in proliferation by observing the consequences of specifically inhibiting its translation in SCLC and neuroepithelioma cells. Finally, the new proto-oncogene (pks) sequence we previously characterized has been mapped by somatic cell hybrids and in situ hybridization to Xp11.2-11.4. A related sequence was also found on chromosome 7, near the centromere.
