10955775

pubmed:Citation

8

Previous studies have shown that the expression of the cell-cell adhesion molecule (C-CAM1), located at chromosome 19, is down-regulated in several types of human cancers, including prostate and breast cancers. Two major isoforms of C-CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, are derived from the C-CAM1 gene through alternative splicing. Tumor cells transfected with L-form C-CAM1, which contains a cytoplasmic domain, display significantly lower growth rates and less tumorigenicity in both in vitro and in vivo models compared with untransfected tumor cells, suggesting that L-form C-CAM1 may be a tumor suppressor. The transfection of the cytoplasmic domain of L-form C-CAM1 could also cause suppression of tumor growth, further supporting the role of L-form C-CAM1 in tumorigenesis. In contrast to reports of most of the tumor types tested, Ohwada et al. (Am. J. Respir. Cell Mol. Biol., 11: 214-220, 1994) reported that C-CAM1 was not down-regulated or even up-regulated in lung cancer. Because the cytoplasmic domain of L-form C-CAM1 is critical for the tumor suppressor function of C-CAM1, we hypothesized that switching of the isoform rather than down- regulation of C-CAM1 gene expression occurs during lung tumorigenesis. To test this hypothesis, we analyzed pairs of tumor tissue and corresponding normal-appearing lung tissue from 51 patients with non-small cell lung cancer (NSCLC) and 43 cell lines to determine expression profiles of L-form C-CAM1 and S-form C-CAM1 using reverse transcription-PCR. We found that L-form C-CAM1 was the predominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most (84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantly S-form C-CAM1 (P < 0.0001). Similarly, 19 (79%) of the 24 NSCLC cell lines and 17 (85%) of the 20 small cell lung cancer cell lines expressed predominantly S-form C-CAM1. The frequent alteration of the C-CAM1 expression pattern suggests that C-CAM1 has an important role in lung tumorigenesis.

eng

IM

MEDLINE

1078-0432

Print

NLM

2988-93

pubmed-meshheading:10955775-Adenosine Triphosphatases, pubmed-meshheading:10955775-Aged, pubmed-meshheading:10955775-Amino Acid Sequence, pubmed-meshheading:10955775-Antigens, CD, pubmed-meshheading:10955775-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:10955775-Carcinoma, Small Cell, pubmed-meshheading:10955775-Cell Adhesion Molecules, pubmed-meshheading:10955775-Female, pubmed-meshheading:10955775-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10955775-Genes, Tumor Suppressor, pubmed-meshheading:10955775-Humans, pubmed-meshheading:10955775-Lung, pubmed-meshheading:10955775-Lung Neoplasms, pubmed-meshheading:10955775-Male, pubmed-meshheading:10955775-Middle Aged, pubmed-meshheading:10955775-Molecular Sequence Data, pubmed-meshheading:10955775-Protein Isoforms, pubmed-meshheading:10955775-Protein Structure, Tertiary, pubmed-meshheading:10955775-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10955775-Tumor Cells, Cultured

C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary lung cancers.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't