Abstract C96: Thyroid hormone induced Beta-catenin-dependent proliferation in colorectal cancer cells

Abstract

Abstract Thyroid hormone has been shown to induce proliferation of a variety of human cancer cell lines via a cell surface binding site on integrin αvβ3. Clinical studies indicate that thyroid hormone may support the growth of brain tumor, breast cancer, head-and-neck cancer, renal cell carcinoma and several other cancers. The effect of microenvironmental thyroid hormone on the growth of colorectal cancer has not been investigated fully. Numerous evidences suggest that the Wnt/β-catenin pathway, which is involved in both normal and oncogenic developments of the gut, is associated with thyroid hormone and its downstream signaling. The study is therefore aimed to look at the role of thyroid hormone, thyroxine (T4) on colon cancer progression through β-catenin activation. Materials and Methods: The effect of T4 in two APC mutant colon cancer cell lines HT-29 and Colo205 cells and one APC wild type colon cancer HCT116 cells were studied. MTT assays were performed to evaluate cell proliferation under different concentrations of T4. Relative mRNA and protein expressions of relevant genes were examined using qPCR and Western blotting, respectively. Results: T4 (10−8 to 10−6 M) induced proliferation in colorectal cancer HT-29 cells, HCT116 cells and Colo205 cells in a concentration-dependent manner. In HT29 and Colo205 cancer cell lines, the expressions of β-catenin and HMGA2 were not significantly altered by the application of T4. Alternatively, T4 increased accumulation of nuclear β-catenin and HMGA2 in HT-29 cells. Nuclear β-catenin and message were elevated by T4 in Colo205 cells. On the other hand, in addition to the cell proliferation and nuclear accumulation of β-catenin and HMGA2, T4 (10−8-10−6 M) induced the expression of β-catenin and HMGA2 in HCT116 cells. The expression of genes involved in proliferation was enhanced by thyroxine treatment. Conclusions: T4 promoted proliferation in colon cancer HT-29, Colo205 and HCT116 cells. The effect of T4 in colon cancer involved nuclear distribution of β-catenin and its activation. However, the different phenotypes of APC affected the accumulation of nuclear β-catenin and HMGA2 induced by T4. Further study concerning detailed mechanisms is required to elucidate the role of thyroid hormone in colon cancer progression. By understanding the mechanisms behind the pathogenic effects of thyroid hormone, we will propose and develop new treatment approaches to colorectal cancers. Citation Format: Hung-Yun Lin. Thyroid hormone induced Beta-catenin-dependent proliferation in colorectal cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C96.