T. Zusman et al., CONTRIBUTION OF THE INTRACELLULAR DOMAIN OF MURINE FC-GAMMA RECEPTOR-TYPE IIB1 TO ITS TUMOR-ENHANCING POTENTIAL, International journal of cancer, 68(2), 1996, pp. 219-227
We have previously shown that Fc gamma receptor type II B1 (Fc gamma R
IIB1), when expressed on non-lymphoid tumor cells, significantly enhan
ced their tumorigenic phenotype. This study elucidates the role of the
intracellular domain of Fc gamma RIIB1 in the enhancement of the mali
gnant phenotype of polyoma-transformed 3T3 cells. We investigated the
tumorigenic potential conferred by different variants of the receptor:
Fc gamma RIIB1, a full-length receptor (B1) whose intracellular regio
n is encoded by exons 8, 9 and 10; Fc gamma RIIB2, a spliced variant (
B2) whose cytoplasmic domain comprises exons 9 and 10 and lacks exon 8
; and Fc gamma RIIB1-CT53, a deleted mutant whose cytoplasmic domain c
ontains the fragment encoded by exon 8 alone. We have investigated var
ious properties of cells transfected with each of the above variants:
tumorigenicity in syngeneic mice, formation of colonies in soft agar,
growth rate, production of soluble receptor and capping of the ligand-
bound receptor. Results show that while the presence of exon 8 did not
enhance growth rate in vitro or production of soluble Fc gamma R, it
did enhance the tumorigenic phenotype of transfected cells (both in vi
vo and in vitro growth in soft agar). B1-expressing cells exhibited a
significantly higher tumorigenic phenotype than B2 cells. The presence
of exon 8 alone (CT53 mutant) conferred the transfected cells a highe
r tumorigenic phenotype than Fc gamma R-negative control cells but low
er than intact B1 or B2 cells, indicating that the presence of B1-spec
ific exon 8 is not sufficient but that the presence of an intact B1 in
tracellular domain is essential, for conferring the high tumorigenicit
y phenotype upon cells. We conclude that the capping, following ligand
binding contributed by exon 8, and the function contributed by the sp
ecific localization of exons 9 and 10 in B1 cells may determine their
malignant phenotype. (C) 1996 Wiley-Liss, Inc.