Consistent loss of functional transforming growth factor beta receptor expression in murine plasmacytomas
Abstract
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 ...Continue Reading
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