Functional validation of genes implicated in lymphomagenesis: an in vivo selection assay using a Myc-induced B-cell tumor.

Abstract:

:The involvement of the c-Myc transcription factor in neoplastic transformation is well documented. However, which of its numerous target genes are crucial for tumorigenesis remains a frequently contested issue. We have recently established a non-transgenic murine model for B-cell lymphoma based on neoplastic conversion of p53-null bone marrow cells by conditionally active Myc. Using this model, we have identified a number of genes whose expression levels are affected by Myc during B-lymphomagenesis. Here we discuss their possible roles in neoplastic processes and describe an experimental approach allowing in vivo validation of these roles. We demonstrate that lymphoma cells overexpressing one of the Myc targets, the interleukin-10 receptor gene, have a very strong selective advantage over low IL10R expressors. Furthermore, Mcl1, a presumptive IL10R effector, also confers selective advantages when overexpressed in Myc-transformed hematopoietic cells. Thus, both IL10R and Mcl1 might be amenable to therapeutic interventions, and new targets can be identified and validated using the selection approach.

journal_name

Ann N Y Acad Sci

authors

Yu D,Cozma D,Park A,Thomas-Tikhonenko A

doi

10.1196/annals.1339.047

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

145-59

eissn

0077-8923

issn

1749-6632

pii

1059/1/145

journal_volume

1059

pub_type

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