Consistent loss of functional transforming growth factor beta receptor expression in murine plasmacytomas.
Murine plasmacytomas are tumors of Ig-secreting plasma cells that can be induced in genetically susceptible BALB/c mice. The deregulation of the c-myc protooncogene is a critical oncogenic event in the development of plasmacytomas (PCTs) although it is not sufficient for their malignant transformation. We have demonstrated that PCTs produce active transforming growth factor beta (TGF-beta) in vitro. Because TGF-beta is a potent negative regulator of the proliferation and differentiation of B lymphocytes, we examined its role in plasmacytomagenesis by comparing responsiveness to TGF-beta of nonneoplastic plasma cells and PCTs. The nontransformed plasma cells that accumulate in interleukin 6 transgenic mice undergo accelerated apoptosis upon treatment with TGF-beta, but the 15 PCTs studied, including primary and transplanted tumors as well as established cell lines, were refractory to TGF-beta-mediated growth inhibition and apoptosis. Although PCTs lack functional TGF-beta receptors as demonstrated by chemical crosslinking to radiolabeled TGF-beta1, they nonetheless contain mRNA and protein for both type I and II TGF-beta receptors, suggesting a potential defect in receptor trafficking or processing. The results clearly show the consistent inactivation of TGF-beta receptors in plasmacytoma cells, demonstrating for the first time that interruption of a tumor suppressor pathway contributes to plasmacytomagenesis.
Amoroso
S R
SR
Laboratories of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055, USA.
Huang
N
N
Roberts
A B
AB
Potter
M
M
Letterio
J J
JJ
D000818:Animals; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010954:Plasmacytoma / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D018125:Receptors, Transforming Growth Factor beta