LINEAGE-SPECIFIC MARKER AND PROTO-ONCOGENE EXPRESSION IN HUMAN LUNG CANCER

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Summary of Work A) CPK-BB - Creatine phosphokinase BB isoenzyme is present in small cell lung cancer as compared to other histologic types. Using a CPK-B clone derived in rabbits, human cDNA clones were generated from a SCLC cDNA library. Use of the isozyme- specific probe confirmed increased expression of CPK-BB at the transcriptional level in small cell as opposed to non-small cell lung cancer. Using the isozyme specific probe, CPK-B was unexpectedly shown to have two different chromosomal locations in humans, suggesting two CPK-B genes. A genomic library from human placenta has yielded genomic clones whose structure is being defined. Definition of the promoter region will allow examination of the factor(s) present in neuroendocrine tissue which mediate the abundant expression of this gene. B) Neuron-Specific Enolase - Further characterization of the clones derived during the past year suggests at least three types of enolase-related genes have been cloned. The precise structure of these genes is being pursued. C) EGF-Receptor Gene Expression - Having defined in the past which non-small cell lung cancer cell lines express the EGF receptor, efforts are now focusing on evidence for receptor function. Experiments suggest that there is evidence of EGF- receptor kinase stimulation by EGF and TGF-. Further studies are to focus on whether this response can be specifically blocked by antibodies to the EGF receptor. D) Ras Gene Expression - Efforts were made to correlate the expression of ras genes with the response of some cell cancer lines to release Ca2+. Further work will focus on whether the ras genes present in these cell lines are germ line or mutated at positions known to promote tumorigenesis.