Using techniques of molecular biology, we studied the amplification and expression of several oncogenes (such as c-myc, N-myc, L-myc, and p53) in small cell and non-small cell lung cancer cell lines and human tissue specimens. The technique of in situ hybridization allowed us to analyze oncogene expression at the cellular level in fixed histopathologic specimens. We have isolated a new oncogene, L-myc, by virtue of its homology to c-myc and N-myc. We have analyzed the structure of L-myc by sequencing cDNA clones derived from tumor cell lines. We have identified a rearrangement involving this oncogene in one tumor cell line. Gene mapping studies in collaboration with Dr. W. McBride at NIH and Dr. I. Kirsch in our branch assigned L-myc to human chromosome region 1p32, a location distinct from c-myc or N-myc. The expression of L-myc during murine development was characterized in collaboration with Columbia University. To study the function of L-myc, we have transfected constructs of this gene alone and with other oncogenes (such as c-Ha-ras) in rat embryo fibroblasts. We have constructed a fusion protein to allow development of monoclonal antibodies to the L-myc gene product. We have previously published data which demonstrates that bombesin/gastrin releasing peptide (BN/GRP) can function as an autocrine growth factor for human small cell lung cancer (SCLC). Using a monoclonal antibody to the carboxy-terminal region of BN/GRP we were able to block endogenous peptide/receptor interaction which in turn caused the cessation of SCLC growth in vitro and in vivo. This antibody designated as MoAb2A11, has been further characterized in other cell systems for its ability to inhibit BN/GRP mediated biological processes.
