Contribution of the intracellular domain of murine Fc-gamma receptor type IIB1 to its tumor-enhancing potential.
We have previously shown that Fc gamma receptor type II B1 (Fc(gamma)RIIB1), when expressed on non-lymphoid tumor cells, significantly enhanced their tumorigenic phenotype. This study elucidates the role of the intracellular domain of Fc(gamma)RIIB1 in the enhancement of the malignant 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 region 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 contains the fragment encoded by exon 8 alone. We have investigated various 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 vivo 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 higher tumorigenic phenotype than Fc(gamma)R-negative control cells but lower than intact B1 or B2 cells, indicating that the presence of B1-specific exon 8 is not sufficient but that the presence of an intact B1 intracellular domain is essential, for conferring the high tumorigenicity phenotype upon cells. We conclude that the capping, following ligand binding contributed by exon 8, and the function contributed by the specific localization of exons 9 and 10 in B1 cells may determine their malignant phenotype.
Zusman
T
T
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Lisansky
E
E
Arons
E
E
Anavi
R
R
Bonnerot
C
C
Sautes
C
C
Fridman
W H
WH
Witz
I P
IP
Ran
M
M
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D018450:Disease Progression; D005260:Female; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000209:etiology*; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014410:Tumor Stem Cell Assay
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D017452:Receptors, IgG