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 ∼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/β‐catenin signaling in 293 cells and in gastric cancer cells. However, while we did find increased expression of a subset of β‐catenin target genes in TC‐1 over expressing cells, we did not find an association of TC‐1 with global expression of β‐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. © 2007 Wiley‐Liss, Inc.