Thyroid Hormone Promotes β-Catenin Activation and Cell Proliferation in Colorectal Cancer

Thyroid hormone status has long been implicated in cancer development. Here we investigated the role of thyroxine (T₄) in colorectal cancer cell lines HCT 116 (APC wild type) and HT-29 (APC mutant), as well as the primary cultures of cancer cells derived from patients. Cell proliferation was evaluated with standard assay and proliferation marker expression. β-Catenin activation was examined according to nuclear β-catenin accumulation and β-catenin target gene expression. The results showed that T₄ increased colorectal cancer cell proliferation while cell number and viability were elevated by T₄ in both established cell lines and primary cells. Moreover, the transcriptions of proliferative genes PCNA, CCND1, and c-Myc were enhanced by T₄ in the primary cells. T₄ induced nuclear β-catenin accumulation, as well as high cyclin D1 and c-Myc levels compared to the untreated cells. In addition, the β-catenin-directed transactivation of CCND1 and c-Myc promoters was also upregulated by T₄. CTNNB1 transcription was raised by T₄ in HCT 116, but not in HT-29, while the boosted β-catenin levels were observed in both. Lastly, the T₄-mediated gene expression could be averted by the knockdown of β-catenin. These results suggested that T₄ promotes β-catenin activation and cell proliferation in colorectal cancer, indicating that an applicable therapeutic strategy should be considered.