Retroviral infection of the FGF2 gene into MCF-7 cells induces branching morphogenesis, retards cell growth and suppresses tumorigenicity in nude mice

FGF2 (basic fibroblast growth factor) is a multifunctional growth factor an d exhibits diverse function in different cell types. In breast, loss of FGF 2 expression is associated with malignant progression. In order to understa nd the role of FGF2 in maintenance of normal breast structures and control of cell growth, we restored FGF2 expression in the breast cancer cell line MCF-7. The FGF2 retrovirally infected MCF-7 cells (MCF-7.F2.5) not only exp ressed FGF2 in cytoplasm and nuclei, but also released FGF2 into culture me dium both on plastic and in Matrigel conditions. The MCF-7.F2.5 cells forme d branches in Matrigel and this effect was abolished by the addition of a n eutralising anti-FGF2 antibody or function blocking antibodies to alpha2, a lpha3 and beta1 integrins. Furthermore, MCF-7.F2.5 cells lost their ability for anchorage-independent growth in soft agar. When MCF-7 and MCF-7.F2.5 c ells were injected into nude mice, there was a 1.6- to 3.2-fold reduction o f tumour volume with MCF-7.F2.5 cells in comparison with the parental MCF-7 cells. MCF-7.F2.5 cells also demonstrated a reduction in oestrogen recepto r-alpha (ER alpha) bath. In vitro and in vivo. Our results suggest that int roduction of the FGF2 gene into MCF-7 cells altered the malignant tumour ce lls towards a more benign phenotype bl vitro and in vivo. (C) 2001 Elsevier Science Ltd. All rights reserved.