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Stem Cells 2006 Dec;24(12):2611-7

Transforming growth factor-beta1 sensitivity is altered in Abl-Myc- and Raf-Myc-induced mouse pre-B-cell tumors.

Letterio J, Rudikoff E, Voong N, Bauer SR

Bauer SR (reprint author), US FDA, Ctr Biol Evaluat & Res, Cell & Tissue Therapy Branch, NIH Bldg 29B,Room 2NN10,HFM-740,1401 Rockville Pi, Rockville, MD 20852 USA US FDA, Ctr Biol Evaluat & Res, Cell & Tissue Therapy Branch, Rockville, MD 20852 USA Case Western Reserve Univ, Div Pediat Hematol Oncol, Ireland Canc Ctr, Cleveland, OH 44106 USA NCI, NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA


Understanding the mechanisms leading to transformation of early B-lineage precursors is an important step leading to rational design of new treatments for precursor (pre)-B-cell leukemia. We used normal mouse pre-B cells to determine if and how transforming growth factor (TGF)-beta1 affects these precursors to the B-cell lineage and whether transformed pre-B cells respond to TGF-beta1. We found that normal pre-B cells proliferating in the presence of interleukin (IL)-7 enter cell-cycle arrest after exposure to TGF-beta1. However, clonally related IL-7-independent tumors induced by oncogenes abl + myc or raf + myc have reduced sensitivity to TGF-beta1. In contrast, tumor cells induced by myc alone remain sensitive to TGF-beta1 growth suppression. These results suggest that lesions in different molecular signaling pathways can lead to loss of TGF-beta1 sensitivity in a single cell type. The approach of using normal pre-B-cell lines and transformation by overexpression of different oncogenes provides a system to compare and contrast molecular pathways that lead to full malignancy.

Category: Journal Article
PubMed ID: #16945999
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29