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

Precious studies have shown that the expression of the cell-cell adhesion m olecule (C-CAM1), located at chromosome 19, is down-regulated in several ty pes of human cancers, including prostate and breast cancers. Two major isof orms of C-CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, a re derived from the C-CAM1 gene through alternative splicing. Tumor cells t ransfected 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 cytoplasm ic domain of L-form CCAM1 could also cause suppression of tumor growth, fur ther 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. Ce ll Mel. Biol,, ZI: 214-220, 1994) reported that C-CAM1 was not down-regulat ed 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 hy pothesized that switching of the isoform rather than down-regulation of C-C AM1 gene expression occurs during lung tumorigenesis, To test this hypothes is, we analyzed pairs of tumor tissue and corresponding normal-appearing lu ng tissue from 51 patients with non-small cell lung cancer (NSCLC) and 43 c ell lines to determine expression profiles of L-form C-CAM1 and S-form C-CA M1 using reverse transcription-PCR. We found that L-form C-CAMI was the pre dominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most (84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantl y S-form C-CAMI (P < 0.0001), Similarly, 19 (79%) of the 24 NSCLC cell line s and 17 (85%) of the 20 small cell lung cancer cell lines expressed predom inantly S-form C-CAMI. The frequent alteration of the 6-CAM1 expression pat tern suggests that C-CAM1 has an important role in lung tumorigenesis.