Haematopoietic progenitor cells transfected with a differentiation antigen show cellular transformation and tumour growt in mice

摘要

A stromal cell line, D064, derived from canine bone marrow stroma, was established and differentiates into haematopoietic progenitors under the influence of growth factor signalling. While differentiating, these cells start to express MHC class II molecules (HLA-DR homologues) on their surface. The transfection of these fibroblast-like cells with retroviral constructs containing the canine MHC class II DR-genes (DRA and DRB) induces a change in morphology, alteration of cell cycle progression and tumour formation in nude mice. Transfected cells are smaller than untransfected parental cells and do not require adherence (anchorage dependent growth). The doubling time of untransfected cells was reduced by more than half, as a sign of accelerated cell cycle progression. Injected subcutaneously into nude mice the DR⁺ transfected cells formed solid tumours, while untransfected cells showed no sign of tumour formation. The transfection-induced changes were seen only with constructs carrying the open reading frame of DRA plus DRB in the correct orientation and expressing the complete DR-dimer on the cell surface. Constructs with DRA and DRB in reverse orientation or vectors without any insert did not differ from the parental cells. These observations suggest that mechanisms normally controlling cell cycle and differentiation can be disrupted by the constitutive transcription and expression of differentiation antigens.