CELL DENSITY-DEPENDENT MODULATION OF BASIC FIBROBLAST GROWTH-FACTOR EXPRESSION BY HUMAN INTERFERON-BETA

The production of basic fibroblast growth factor (bFGF) by human renal cell carcinoma (HRCC) is associated with induction of angiogenesis. I ncubation of HRCC cells with human interferon alpha (IFN-alpha) or int erferon beta (IFN-beta) downregulates the expression of bFGF and, henc e, angiogenesis. The purpose of this study was to analyze the downregu lation of the expression of bFGF in HRCC cells by IFN-alpha and IFN-be ta. Human HRCC SN12PM6 cells cultured under sparse conditions expresse d 3-7-fold higher levels of steady-state bFGF-specific mRNA transcript s and cellular bFGF protein than did confluent cultures. IFN-alpha or IFN-beta inhibited the steady-state expression of bFGF mRNA transcript s and cellular bFGF protein in a concentration-dependent manner in spa rse but not confluent cultures. Moreover, IFN-beta downregulated the t ranscription rate of bFGF genes and inhibited the de novo synthesis of bFGF protein only in sparse cultures. The results demonstrate that th e inhibitory effects of IFN- and -beta on bFGF expression are cell-den sity dependent.