The tumor growth-inhibiting cell adhesion molecule CEACAM1 (C-CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation

The hemophilic cell adhesion molecule CEACAM1 (C-CAM, BGP, CD66a) occurs as two coexpressed isoforms, CEACAM1-L and CEACAM1-S, in epithelia, endotheli a, and leukocytes, CEACAM1-L can inhibit tumor growth; this effect is influ enced by CEACAM1-S. To characterize the growth regulatory properties of CEA CAM1, we analyzed the expression patterns of the isoforms, and here we demo nstrate that both the expression levels and the S:L isoform ratios differ i n proliferating and quiescent rat epithelial cells. Quiescent prostate NbE cells expressed more CEACAM1 than quiescent bladder NET-II cells, a pattern that correlated with the expression levels in the parental tissues, In con trast, both the expression levels and the isoform ratios were strikingly si milar in proliferating NbE and NET-II cells, showing that a particular CEAC AM1 expression pattern is compatible with cell proliferation. However, in c onfluent cells, CEACAM1 seemed to exert inhibitory effects on cell prolifer ation. Addition of anti-CEACAM1 antibodies to quiescent, confluent cells ca used decreased expression of the cyclin-dependent kinase inhibitor, p27(Kip 1), stimulated growth factor-dependent DNA synthesis, and altered the S:L i soform ratio toward the ratio characteristic of proliferating cells. Taken together, our data suggest that CEACAM1 contributes to contact inhibition o f cell proliferation in confluent cells but allows proliferation when expre ssed at different isoform ratios.