Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor pathway and its involvement in colorectal carcinogenesis.

Abstract

To elucidate the molecular mechanism of colorectal carcinogenesis, we have been attempting to isolate genes involved in the beta-catenin/T-cell factor pathway. In the experiments reported here, analysis by cDNA microarray indicated that AF17, a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21), was transactivated according to accumulation of beta-catenin. Expression of AF17 was significantly enhanced in 8 of the 12 colorectal cancer tissues examined. Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3 cells, and fluorescence-activated cell sorter analysis indicated that the AF17 regulation of cell-cycle progression was occurring mainly at the G(2)-M transition. Our results suggest that the AF17 gene product is likely to be involved in the beta-catenin-T-cell factor/lymphoid enhancer factor signaling pathway and to function as a growth-promoting, oncogenic protein. These findings should aid development of new strategies for diagnosis, treatment, and prevention of colon cancers and acute leukemias by clarifying the pathogenesis of these conditions.

• Authors: Y M Lin, K Ono, S Satoh, H Ishiguro, M Fujita, N Miwa, T Tanaka, T Tsunoda, K C Yang, Y Nakamura, Y Furukawa
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 17 Pg. 6345-9 (Sep 01 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11522623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, human
• CTNNB1 protein, mouse
• Cytoskeletal Proteins
• DNA-Binding Proteins
• Lymphoid Enhancer-Binding Factor 1
• MLLT6 protein, human
• Mllt6 protein, mouse
• Neoplasm Proteins
• Trans-Activators
• Transcription Factors
• beta Catenin

Topics

• 3T3 Cells
• Animals
• COS Cells
• Cell Cycle (physiology)
• Cell Division (physiology)
• Chlorocebus aethiops
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Cytoskeletal Proteins (physiology)
• DNA-Binding Proteins (physiology)
• Humans
• Lymphoid Enhancer-Binding Factor 1
• Mice
• Neoplasm Proteins (biosynthesis, genetics, physiology)
• Oligonucleotide Array Sequence Analysis
• Signal Transduction (physiology)
• Trans-Activators
• Transcription Factors (physiology)
• Transcription, Genetic
• Transcriptional Activation
• Transfection
• Tumor Cells, Cultured
• beta Catenin