IDENTIFICATION OF MOLECULAR MARKERS FOR HUMAN LUNG CANCER

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We have used the differential display method to isolate a novel gene, N8, which expresses a 2.4 Kb mRNA at higher levels in lung tumor cells than normal cells. N8 mRNA contains a 552 nucleotide open reading frame (ORF) which encodes a 184 amino acid protein. In kidney, we have identified a larger ORF (N8L) encoding a 248 amino acid protein which has an extra 64 amino acids immediately to the N-terminal of N8 protein. Using somatic cell hybrid panel and fluorescence in situ hybridization (FISH) techniques, we have localized the N8 gene to human chromosome 8q13 region. N8 mRNA is present at high levels in human adult kidney, brain, small intestine, prostate, and pancreas. It is expressed at moderate levels in adult colon and placenta, and at low levels in several other tissues, including lung. The N8 gene is specifically expressed in the gut, nasal epithelia, areas surrounding eyes, and salivary glands in either 18 day-old embryo or one day-old newborn mice, suggesting the N8 gene may be developmentally regulated and may play different roles during embryogenesis and in adult stage. N8 protein is a hydrophilic, cytoplasmic protein capable of forming homodimers. N8 protein is present at very high levels in lung tumor cell lines and very low levels in normal lung tissue-derived cell lines. It is also present in many other tumor cell lines, including breast, colon, prostate, and brain cancer and leukemia cell lines. N8 protein has limited homology to some cytoskeleton-related proteins, such as myosin heavy chain, microtubule-vesicle linker CLIP-170, US01 intracellular transport protein and intermediate filament-associated protein restin. N8 could be used as a potential molecular marker for lung cancer.