HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2005-0623v1 24/12/2611    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Letterio, J. Articles by Bauer, S. R. Search for Related Content PubMed PubMed Citation Articles by Letterio, J. Articles by Bauer, S. R.

CANCER STEM CELLS

Transforming Growth Factor-ß1 Sensitivity Is Altered in Abl-Myc- and Raf-Myc-Induced Mouse Pre-B-Cell Tumors

^aCase Western Reserve University, Division of Pediatric Hematology/Oncology, The Ireland Cancer Center, Cleveland, Ohio, USA;
^bFood and Drug Administration, Center for Biologics Evaluation and Research, Cell and Tissue Therapy Branch, Rockville, Maryland, USA;
^cNational Institutes of Health, National Cancer Institute, Laboratory of Cell Regulation and Carcinogenesis, Bethesda, Maryland, USA

Key Words. Transforming growth factor-ß1 • Pre-B tumors • myc • abl • raf

Correspondence: Steven R. Bauer, Ph.D., Food and Drug Administration, Center for Biologics Evaluation and Research, Cell and Tissue Therapy Branch, NIH Bldg 29B, Room 2NN10, HFM-740, 1401 Rockville Pike, Rockville, Maryland 20852, USA. Telephone: 301-827-0684; Fax: 301-827-0449; e-mail: Steven.Bauer{at}fda.hhs.gov

Received December 12, 2005; accepted for publication August 19, 2006.
First published online in STEM CELLS EXPRESS   August 31, 2006.



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)-ß1 affects these precursors to the B-cell lineage and whether transformed pre-B cells respond to TGF-ß1. We found that normal pre-B cells proliferating in the presence of interleukin (IL)-7 enter cell-cycle arrest after exposure to TGF-ß1. However, clonally related IL-7-independent tumors induced by oncogenes abl + myc or raf + myc have reduced sensitivity to TGF-ß1. In contrast, tumor cells induced by myc alone remain sensitive to TGF-ß1 growth suppression. These results suggest that lesions in different molecular signaling pathways can lead to loss of TGF-ß1 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.