NF-kappaB activation in premalignant mouse tal-1/scl thymocytes and tumors
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDepartment of Cancer Biology
Document Type
Journal ArticlePublication Date
2003-06-21Keywords
AnimalsAntigens, CD4
Antigens, CD8
Basic Helix-Loop-Helix Transcription Factors
DNA-Binding Proteins
Gene Expression Regulation, Leukemic
I-kappa B Proteins
Mice
Mice, Mutant Strains
NF-kappa B
NF-kappa B p50 Subunit
Precancerous Conditions
Precursor Cell Lymphoblastic
Leukemia-Lymphoma
Proto-Oncogene Proteins
T-Lymphocytes
Thymus Gland
Thymus Neoplasms
Transcription Factor RelA
Transcription Factors
Cancer Biology
Microbiology
Molecular Genetics
Metadata
Show full item recordAbstract
TAL-1/SCL activation is a common genetic event in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Expression of tal-1/scl or a DNA binding mutant of tal-1/scl induces arrest of thymocyte development, resulting in decreases in double-positive and single-positive CD4 thymocytes. Moreover, nuclear p65/p50 heterodimers are detected in premalignant tal-1/scl and mut tal-1/scl thymocytes, suggesting that E2A depletion may induce developmental arrest and stimulate NF-kappaB activation. Increased NF-kappaB activity is also observed in tal-1/scl tumors and bcl-2 is overexpressed. To examine the contribution of NF-kappaB to tal-1/scl tumor growth in vivo, we expressed a mutant form of IkappaBalpha in tal-1/scl tumor cells. Although expression of mutant IkappaBalpha inhibited the tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB response, it had no effect on tumor growth in mice. These data suggest that NF-kappaB activation is an early event in tal-1/scl-induced leukemogenesis, associated with arrest of thymocyte development, and does not appear to contribute to tal-1/scl-induced tumor growth.Source
Blood. 2003 Oct 1;102(7):2593-6. Epub 2003 Jun 19. Link to article on publisher's siteDOI
10.1182/blood-2003-01-0090Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39980PubMed ID
12816868Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1182/blood-2003-01-0090