The tumor growth-inhibiting cell adhesion molecule CEACAM1 (C-CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation.
The homophilic cell adhesion molecule CEACAM1 (C-CAM, BGP, CD66a) occurs as two coexpressed isoforms, CEACAM1-L and CEACAM1-S, in epithelia, endothelia, and leukocytes. CEACAM1-L can inhibit tumor growth; this effect is influenced by CEACAM1-S. To characterize the growth regulatory properties of CEACAM1, we analyzed the expression patterns of the isoforms, and here we demonstrate that both the expression levels and the S:L isoform ratios differ in proliferating and quiescent rat epithelial cells. Quiescent prostate NbE cells expressed more CEACAM1 than quiescent bladder NBT-II cells, a pattern that correlated with the expression levels in the parental tissues. In contrast, both the expression levels and the isoform ratios were strikingly similar in proliferating NbE and NBT-II cells, showing that a particular CEACAM1 expression pattern is compatible with cell proliferation. However, in confluent cells, CEACAM1 seemed to exert inhibitory effects on cell proliferation. Addition of anti-CEACAM1 antibodies to quiescent, confluent cells caused decreased expression of the cyclin-dependent kinase inhibitor, p27Klp1, stimulated growth factor-dependent DNA synthesis, and altered the S:L isoform ratio toward the ratio characteristic of proliferating cells. Taken together, our data suggest that CEACAM1 contributes to contact inhibition of cell proliferation in confluent cells but allows proliferation when expressed at different isoform ratios.
Singer
B B
BB
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
Scheffrahn
I
I
Obrink
B
B
D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051381:Rats; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D000251:Adenosine Triphosphatases