Transforming properties of TC-1 in human breast cancer: interaction with FGFR2 and beta-catenin signaling pathways |
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Authors: | Yang Zeng-Quan Moffa Allison B Haddad Ramsi Streicher Katie L Ethier Stephen P |
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Institution: | Breast Cancer Program, Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA. yangz@karmanos.org |
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Abstract: | Breast cancer development is associated with gene amplification and over expression that is believed to have a causative role in oncogenesis. Previous studies have demonstrated that over expression of TC-1(C8orf4) mRNA occurs in approximately 50% of breast cancer cell lines and primary tumor specimens. Here, we show that TC-1 has transforming properties in human mammary epithelial (HME) cells and its expression is mechanistically linked to FGFR signaling cascades. In vitro experiments demonstrate that TC-1 over expression mediates both anchorage-independent and growth factor-independent proliferation of HME cells. TC-1 was down regulated by the FGFR inhibitor PD173074 in the breast cancer cell line SUM-52 that also has an FGFR2 gene amplification and over expression. Furthermore, forced expression of FGFR2 in HME cells increased the level of expression of endogenous TC-1 mRNA. TC-1 has been implicated as a modulator of Wnt/beta-catenin signaling in 293 cells and in gastric cancer cells. However, while we did find increased expression of a subset of beta-catenin target genes in TC-1 over expressing cells, we did not find an association of TC-1 with global expression of beta-catenin target genes in our cells. Taken together, our data suggest that TC-1 over expression is transforming and may link with the FGFR pathway in a subset of breast cancer. |
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Keywords: | TC‐1 FGFR2 breast cancer |
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