differential roles of fibroblast growth factor receptors (fgfr) 1, 2 and 3 in the regulation of s115 breast cancer cell growth微分作用的纤维母细胞生长因子受体(fgfr)1、2和3的监管s115乳腺癌细胞生长.pdfVIP

Differential Roles of Fibroblast Growth Factor Receptors (FGFR) 1, 2 and 3 in the Regulation of S115 Breast Cancer Cell Growth 1,6 . 2. ¨ ¨ 1,7 5 ¨ 3 Kati M. Tarkkonen * , Emeli M. Nilsson , Tiina E. Kahkonen , Julien H. Dey , Jari E. Heikkila , 1,4 2 5 ¨ ¨ 1 Johanna M. Tuomela , Qing Liu , Nancy E. Hynes , Pirkko L. Harkonen 1 Institute of Biomedicine, Department of Cell Biology and Anatomy, University of Turku, Turku, Finland, 2 Department of Laboratory Medicine, Tumor Biology, Lund University, Lund, Sweden, 3 Department of Biochemistry and Pharmacy, Abo Akademi University, Turku, Finland, 4 Pharmatest Services Ltd, Turku, Finland, 5 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland, 6 Turku Graduate School of Biomedical Science, Turku, Finland, 7 FinPharma Doctoral Program, Drug Discovery Section, Turku, Finland Abstract Fibroblast growth factors (FGFs) regulate the growth and progression of breast cancer. FGF signaling is transduced through FGF receptors 1–4, which have oncogenic or anti-oncogenic roles depending on the ligand and the cellular context. Our aim was to clarify the roles of FGFR1–3 in breast cancer cell growth in vitro and in vivo. Pools of S115 mouse breast cancer cells expressing shRNA against FGFR1, 2 and 3 were created by lentiviral gene transfer, resulting in cells with downregulated expression of FGFR1, FGFR2 or FGFR3 (shR1, shR2 and shR3 cells, respectively) and shLacZ controls. FGFR1- silenced shR1 cells formed small, poorly vascularized tumors in nude mice. Silencing of FGFR2 in shR2 cells was associated