Phenotypic alterations in fibroblasts and fibrosarcoma cells that overexpress latent transforming growth factor-beta 1.

Beauchamp RD, Sheng HM, Bascom CC, Miller DA, Lyons RM, Torre-Amione G, Moses HL
Endocrinology. 1992 130 (5): 2476-86

PMID: 1374006 · DOI:10.1210/endo.130.5.1374006

Mouse embryo-derived AKR-2B fibroblasts and murine fibrosarcoma cells (the 1591 cell line) were transfected with a murine transforming growth factor-beta 1 (TGF beta 1) cDNA under the transcriptional control of either the simian virus-40 early promoter or the cytomegalovirus promoter/enhancer. Selected clones secreted 2- to 4-fold more TGF beta-competing activity into their media than the parental cell line or neomycin-transfected controls. The TGF beta 1 released into the cell-conditioned medium was latent. Despite the latency of the overexpressed TGF beta 1, TGF beta 1-transfected cells exhibited phenotypic features of TGF beta 1-treated cells. When confluent, the TGF beta 1-transfected cells had the morphological characteristics of the parental cells that have been treated with active TGF beta 1. AKR-2B cells that expressed higher levels of TGF beta 1 also expressed high levels of c-sis and c-myc mRNAs and decreased TGF beta 2 and TGF beta 3 mRNAs in the same manner as parental AKR-2B cells that had been treated with active TGF beta 1. The transfected 1591 cells that overexpressed TGF beta 1 bound less [125I]TGF beta 1 than did parental 1591 cells, but after a mild acid wash demonstrated an increase in [125I]TGF beta 1 binding. Our results suggest that these TGF beta 1-transfected fibroblast and fibrosarcoma cells have the capacity to activate TGF beta; however, as very little activated TGF beta is detected in the medium, it is hypothesized that these cells activate latent TGF beta 1 and bind the activated TGF beta 1, thus acquiring a phenotype consistent with TGF beta 1-treated cells.

MeSH Terms (21)

Animals Blotting, Northern Cell Line Embryo, Mammalian Fibroblasts Fibrosarcoma Gene Expression Kinetics Mice Mice, Inbred C3H Phenotype Plasmids Poly A Receptors, Cell Surface Receptors, Transforming Growth Factor beta RNA RNA, Messenger Sarcoma, Experimental Suramin Transfection Transforming Growth Factor beta

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