TCF/beta-catenin plays an important role in HCCR-1 oncogene expression

• Published in: BMC molecular biology 2009-05, Vol.10 (42), p.42-42, Article 42
• Main Authors: Cho, Goang-Won, Kim, Mi-Hwa, Kim, Seung Hyun, Ha, Seon-Ah, Kim, Hyun Kee, Kim, Sanghee, Kim, Jin W
• Format: Article
• Language: English
• Subjects: beta Catenin - genetics; beta Catenin - metabolism; Binding Sites; Cell Line; Cervical cancer; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Humans; Identification and classification; Neoplasms - genetics; Neoplasms - metabolism; Oncogenes; Physiological aspects; Promoter Regions, Genetic; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-oncogenes; TCF Transcription Factors - genetics; TCF Transcription Factors - metabolism; Transcriptional Activation
• ISSN: 1471-2199; 1471-2199
• DOI: 10.1186/1471-2199-10-42

Oncogene HCCR-1 functions as a negative regulator of the p53 and contributes to tumorigenesis of various human tissues. However, it is unknown how HCCR-1 contributes to the cellular and biochemical mechanisms of human tumorigenesis. In this study, we showed how the expression of HCCR-1 is modulated. The luciferase activity assay indicated that the HCCR-1 5'-flanking region at positions -166 to +30 plays an important role in HCCR-1 promoter activity. Computational analysis of this region identified two consensus sequences for the T-cell factor (TCF) located at -26 to -4 (Tcf1) and -136 to -114 (Tcf2). Mutation at the Tcf1 site led to a dramatic decrease in promoter activity. Mobility shift assays (EMSA) revealed that nuclear proteins bind to the Tcf1 site, but not to the Tcf2 site. LiCl, Wnt signal activator by GSK-3beta inhibition, significantly increased reporter activities in wild-type Tcf1-containing constructs, but were without effect in mutant Tcf1-containing constructs in HEK/293 cells. In addition, endogenous HCCR-1 expression was also increased by treatment with GSK-3beta inhibitor, LiCl or AR-A014418 in HEK/293 and K562 cells. Finally, we also observed that the transcription factor, TCF, and its cofactor, beta-catenin, bound to the Tcf1 site. These findings suggest that the Tcf1 site on the HCCR-1 promoter is a major element regulating HCCR-1 expression and abnormal stimulation of this site may induce various human cancers.