Expression of transforming growth factor beta type III receptor suppresses tumorigenicity of human breast cancer MDA-MB-231 cells.
Transforming growth factor beta (TGF-beta) promotes tumor progression in some model systems including human breast cancer cells. In this study, we report that human breast cancer cell lines express reduced amounts of TGF-beta type III receptor (RIII) when compared with untransformed human mammary epithelial cells. Consequently, we examined whether expression of RIII in human breast cancer MDA-MB-231 cells could reduce TGF-beta's tumor promoting activity by sequestering active TGF-beta isoforms produced by the cells. A tetracycline-repressible human RIII expression vector was stably transfected into the cell line. RIII expression in a pool of transfected clones and a single clone was found to be reversibly repressed by tetracycline treatment. Expression of RIII reduced the amount of active TGF-beta1 and TGF-beta2 in the conditioned medium. The medium conditioned by control cells showed a significantly higher growth inhibitory effect than that conditioned by RIII-transfected cells on the growth of the mink lung epithelial CCL64 cells. A conditioned medium collected from RIII-transfected cells treated with tetracycline significantly increased its growth inhibitory activity to that of control cells. Expression of RIII also reduced tumor incidence and growth rate in two separate experiments when the cells were inoculated in athymic nude mice. Treatment of the mice with tetracycline repressed RIII expression in the tumors generated by RIII-transfected cells and increased tumor incidence and growth rate. These results suggest that TGF-beta RIII can reduce tumorigenicity of MDA-MB-231 cells apparently by sequestering TGF-beta isoforms produced by these cells.
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Department of Pharmacology, Lucille P. Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
Chen
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D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism; D017077:Culture Media, Conditioned; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008168:Lung; D051379:Mice; D008819:Mice, Nude; D008907:Mink; D011509:Proteoglycans / Q000096:biosynthesis* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis; D013752:Tetracycline / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D011509:Proteoglycans; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C071736:betaglycan; D013752:Tetracycline