Biliary glycoproteins (BGPs) are members of the carcinoembryonic antig
en (CEA) family, These glycoproteins function in vitro as intercellula
r adhesion molecules and, in the mouse, serve as receptors for the mou
se hepatitis viruses, In previous studies, BGP expression has been rep
orted to be generally downregulated in colon and liver carcinomas of h
uman, rat and mouse origins, We now demonstrate that introduction of m
urine Bgp1 cDNA isoforms into a mouse colonic carcinoma cell line, neg
ative for endogenous Bgpl expression, significantly alters the growth
properties of these cells, Cells bearing two Bgpl isoforms were growth
-retarded and exhibited a reduced ability to form colonies in an ill v
itro transformation assay, when compared to parental or control neo(r)
cells, Furthermore, tumor formation was inhibited by 80% when cells b
earing a full-length Bgpl isoform were injected into BALB/c syngeneic
mice, while cells expressing a Bgpl isoform lacking most of the intrac
ytoplasmic domain produced tumors as readily as the parental cells, Th
ese results indicate that a biliary glycoprotein isoform is involved i
n negative regulation of colonic tumor cell growth, by a process which
requires its intracytoplasmic domain, The precise mechanisms causing
Bgp-dependent tumor growth inhibition remain, however, to be defined.