Abstract
In many cancers, inactivation of the adenomatous polyposis coli (APC) or Axin tumor suppressor proteins or activating mutations in beta-catenin lead to elevated beta-catenin levels, enhanced binding of beta-catenin to T cell factor (TCF) proteins, and increased expression of TCF-regulated genes. We found that the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor-2) was activated in rat E1A-immortalized RK3E cells following neoplastic transformation by beta-catenin or ligand-induced activation of a beta-catenin-estrogen receptor fusion protein. Human cancers with beta-catenin regulatory defects had elevated ITF-2 expression, and ITF-2 was repressed by restoring wild-type APC function or inhibiting TCF activity. Of note, ITF-2 promoted neoplastic transformation of RK3E cells. We propose that ITF-2 is a TCF-regulated gene, which functions in concert with other TCF target genes to promote growth and/or survival of cancer cells with defects in beta-catenin regulation.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Cell Transformation, Neoplastic / genetics
-
Cell Transformation, Neoplastic / metabolism*
-
Cytoskeletal Proteins / genetics
-
Cytoskeletal Proteins / metabolism*
-
DNA-Binding Proteins / metabolism*
-
Female
-
Humans
-
Lymphoid Enhancer-Binding Factor 1
-
Mutation / genetics
-
Neoplasms / metabolism*
-
Ovarian Neoplasms / metabolism
-
Ovarian Neoplasms / pathology
-
Proto-Oncogene Proteins / metabolism*
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Rats
-
Reverse Transcriptase Polymerase Chain Reaction
-
Signal Transduction*
-
TCF Transcription Factors
-
Trans-Activators / metabolism*
-
Transcription Factor 4
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors / metabolism*
-
Tumor Cells, Cultured
-
Wnt Proteins
-
Zebrafish Proteins*
-
beta Catenin
Substances
-
CTNNB1 protein, human
-
Ctnnb1 protein, rat
-
Cytoskeletal Proteins
-
DNA-Binding Proteins
-
Lymphoid Enhancer-Binding Factor 1
-
Proto-Oncogene Proteins
-
RNA, Messenger
-
TCF Transcription Factors
-
TCF7L2 protein, human
-
Tcf4 protein, rat
-
Tcf7l2 protein, rat
-
Trans-Activators
-
Transcription Factor 4
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors
-
Wnt Proteins
-
Zebrafish Proteins
-
beta Catenin