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Transforming growth factor-beta1 sensitivity is altered in Abl-Myc- and Raf-Myc-induced mouse pre-B-cell tumors.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2006 Dec; Vol. 24 (12), pp. 2611-7. Date of Electronic Publication: 2006 Aug 31. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Animals
B-Lymphocytes cytology
B-Lymphocytes metabolism
Cell Proliferation drug effects
Cell Transformation, Neoplastic
G1 Phase drug effects
Gene Expression drug effects
Mice
Neoplasms genetics
Oncogene Protein p55(v-myc) metabolism
Oncogene Proteins v-abl metabolism
Oncogene Proteins v-raf metabolism
Receptors, Interleukin-7 metabolism
B-Lymphocytes drug effects
B-Lymphocytes pathology
Neoplasms pathology
Oncogene Protein p55(v-myc) genetics
Oncogene Proteins v-abl genetics
Oncogene Proteins v-raf genetics
Transforming Growth Factor beta1 pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1066-5099
- Volume :
- 24
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 16945999
- Full Text :
- https://doi.org/10.1634/stemcells.2005-0623