Differentially expressed genes associated with human lung cancer.

To investigate the gene expression of 9 cDNA clones generated by suppression subtraction hybridization (SSH), Northern blot analysis was performed on a panel of immortalized bronchial epithelial cell lines, lung cancer cell lines and normal human bronchial epithelial cells (HBEC). The clones were located on chromosomes 1q, 2q, 3p, 3q, 4q and 14q representing regions that are frequently affected by DNA imbalances as shown by comparative genomic hybridization (CGH). Two were unknown (H24, H103) whereas the others matched to the Pest-containing nuclear protein (H52), Rp11-767C1 gene (H134), the hypothetical gene AK025444 (H238), Guanine nucleotide binding protein (G protein)/alpha inhibiting activity polypeptide 2 (H268), Laminin gamma 1 (Y45), the DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 9 (Y162) and the heat shock 90 kDa protein 1, alpha (Y238). Northern blot results indicated that all of the studied clones showed differential up- or down-regulation in immortalized cells and lung cancer cell lines. Of those, clone Y238 representing HSP90alpha showed a clearly over-expressed transcript. Subsequently, semi-quantitative RT-PCR was used to further confirm the over-expression of Y238, indicating that HSP90alpha was significantly over-represented in 49 primary lung tumors as compared to 14 normal lung samples (P<0.01). CGH showed that the majority of studied lung cancer cell lines (71.4%) carried an overrepresentation at 14q32 where HSP90alpha is located suggesting that it may be affected by DNA copy number changes. The further characterization of these clones will provide us with valuable information on its role in lung carcinogenesis and may help to develop new diagnostic or therapeutic targets for this lethal disease.