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

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A "fingerprint" of the genes expressed in different types of human lung cancer would be of value in delineating prognostic groups and in characterizing distinctive biologic features. Small cell lung cancer (SCLC) is distinctive in that neuroendocrine characteristics are unique to this group of malignancies, in contrast to different yet distinctive non-neuroendocrine characters of other histologic subtypes. To acquire reagents to understand the basis of these distinctions, the following molecular clones were derived: A) CPK-BB. Creatine phosphokinase B B is an enzyme known to be present in abundant quantities in SCLC. Using a CPK-B clone derived from rabbit, human probes were generated from a SCLC cDNA library and a region unique to CPK-B identified in the 3' untranslated region. This was used to demonstrate differential expression at the level of transcription in SCLC as opposed to non-SCLC lines. The studies demonstrated the utilization of this region of the cDNA as a specific probe for the human isoenzyme, and allowed preliminary analysis of the genomic structure of CPK-B. The probe will be used to map the chromosomal location, and ultimately the full length cDNA or equivalent full length clone will be used to transfect into recipient cells and determine the alteration of host metabolism subsequent to CPK increase. B) Neuron-Specific Enolase. Using a fragment of putative rat NSE cDNA, a SCLC library was screened and yielded a clone which has the appropriate site and tissue distribution for an expected human clone. Further characterization has confirmed sequence homology with rat cDNA, and studies of the basis for differentiated tissue expression will proceed.