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. Incubation of HRCC cells with human interferon alpha (IFN-alpha) or interferon beta (IFN-beta) downregulates the expression of bFGF and, hence, angiogenesis. The purpose of this study was to analyze the downregulation of the expression of bFGF in HRCC cells by IFN-alpha and IFN-beta. Human HRCC SN12PM6 cells cultured under sparse conditions expressed 3-7-fold higher levels of steady-state bFGF-specific mRNA transcripts and cellular bFGF protein than did confluent cultures. IFN-alpha or IFN-beta inhibited the steady-state expression of bFGF mRNA transcripts and cellular bFGF protein in a concentration-dependent manner in sparse but not confluent cultures. Moreover, IFN-beta downregulated the transcription rate of bFGF genes and inhibited the de novo synthesis of bFGF protein only in sparse cultures. The results demonstrate that the inhibitory effects of IFN- and -beta on bFGF expression are cell-density dependent.