C. Turbide et al., OPTIMAL RATIOS OF BILIARY GLYCOPROTEIN ISOFORMS REQUIRED FOR INHIBITION OF COLONIC TUMOR-CELL GROWTH, Cancer research, 57(13), 1997, pp. 2781-2788
Rodent biliary glycoprotein (Bgp), also known as C-CAM, has recently b
een shown to function as a tumor suppressor in colon, prostate, and bl
adder cancers. This glycoprotein is a member of the carcinoembryonic a
ntigen family and is one of the only proteins in this family to encode
either a long (71-73 amino acids) or short (10 amino acids) cytoplasm
ic domain. We and others have shown that the growth-inhibitory propert
ies of Bgp depend upon the expression of its long cytoplasmic domain.
However, the two Bgp isoforms normally coexist in most cell types surv
eyed; the longer variant is usually present in lower amounts than the
shorter one. In this study, we have examined the in vitro and in vivo
growth properties of both mouse Bgp variants separately and in combina
tion. To determine the physiologically relevant expression levels and
ratios of the two Bgp variants, we have quantified the amount of the l
onger variant in normal colonic epithelial cells and showed that it co
nstitutes 15-20% of total Bgp expressed in this tissue. To mimic the i
n vivo situation, we have generated double transfectant cell lines exp
ressing the longer and shorter Bgp isoforms coordinately in tumorigeni
c CT51 mouse colonic carcinoma cells and demonstrated that the longer
Bgp isoform exhibits a dominant tumor growth inhibition phenotype over
that of the shorter variant within physiological levels of expression
of Bgp. Unexpectedly, significant overexpression of the longer Bgp is
oform alone led to reversal of the tumor inhibition phenotype. These r
esults, therefore, suggest that there may be a limiting threshold of B
gp expression or Bgp-associating proteins mediating the tumor inhibiti
on phenotype.