TGF1 sensitivity is altered in abl-myc and raf-myc induced mouse pre-B cell tumors

¹ Division of Pediatric Hematology/Oncology, Case Western Reserve University, Cleveland, Ohio
² Cell and Tissue Therapy Branch, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland
³ National Cancer Institute, National Institutes of Health, Bethesda, Maryland

^* To whom correspondence should be addressed. E-mail: steven.bauer{at}fda.hhs.gov.

	Abstract

Understanding the mechanisms leading to transformation of early B-lineage precursors is an important step leading to rational design of new treatments for pre-B cell leukemia. We used normal mouse pre-B cells to determine if and how TGF-1 affects these precursors to the B-cell lineage and whether transformed pre-B cells respond to TGF-1. We found that normal pre-B cells proliferating in the presence of IL-7 enter cell cycle arrest after exposure to TGF-1. However, clonally related, IL-7 independent tumors induced by oncogenes abl + myc or raf + myc have reduced sensitivity to TGF-1. In contrast, tumor cells induced by myc alone remain sensitive to TGF-1 growth suppression. These results suggest that lesions in different molecular signaling pathways can lead to loss of TGF-1 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.

Key Words. TGF-1, pre-B tumors, myc, abl, raf