Transforming properties of TC-1 in human breast cancer: interaction with FGFR2 and beta-catenin signaling pathways.

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.

• Authors: Zeng-Quan Yang, Allison B Moffa, Ramsi Haddad, Katie L Streicher, Stephen P Ethier
• Journal: International journal of cancer (Int J Cancer) Vol. 121 Issue 6 Pg. 1265-73 (Sep 15 2007) ISSN: 0020-7136 [Print] United States
• PMID: 17520678 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• CTNNB1 protein, human
• Neoplasm Proteins
• PD 173074
• Pyrimidines
• RNA, Messenger
• RNA, Small Interfering
• TCIM protein, human
• beta Catenin
• FGFR2 protein, human
• Receptor, Fibroblast Growth Factor, Type 2

Topics

• Animals
• Blotting, Northern
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics, metabolism)
• Female
• Gene Amplification
• Gene Expression (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects, physiology)
• Humans
• Mice
• Neoplasm Proteins (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Pyrimidines (pharmacology)
• RNA, Messenger (analysis)
• RNA, Small Interfering
• Receptor, Fibroblast Growth Factor, Type 2 (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)
• beta Catenin (genetics, metabolism)