Direct effect of basic fibroblast growth factor on gene transcription in a cell-free system.

Abstract

Recent findings on the translocation of intact fibroblast growth factor (FGF) into the cell nucleus suggest that it functions directly in nuclear events. We examined the effect of human basic FGF (bFGF) on gene transcription in a cell-free system. When mouse genes encoding phosphoglycerate kinases 1 and 2 (Pgk-1 and Pgk-2) were transcribed by using nuclear extracts of Ehrlich ascites tumor cells, FGF affected transcription in different ways: in the presence of bFGF, transcription of the Pgk-1 gene was inhibited, whereas that of the Pgk-2 gene was enhanced. When viral genes were tested, transcription of the adenovirus major late DNA was slightly stimulated but that of the adenovirus early EIA DNA or the human immunodeficiency virus DNA was not changed by the addition of bFGF. Moreover, the presence of a distinct 5' upstream region of the Pgk-2 gene, which includes a negative cis-acting element, was required for transcription stimulation by bFGF. These results suggest that bFGF can regulate transcription directly in the nucleus in a gene-specific manner.

Effect of Basic Fibroblast Growth Factor on Synthesis/Secretion of pS2 Protein by Human Breast Cancer Cells (MCF‐7)

“…Further studies are necessary to assess more precisely the mechanism of induction of pS2 protein by use of the nuclear run-on assay. Recently, bFGF, which has its receptor on the surface of the plasma membrane, was shown to become localized in the nucleus as its functional form in many cultured cells and tissues and to directly regulate the transcription of some genes in a cell-free system [31]. But the present results ruled out the possibility that bFGF directly regulates the transcription of pS2 gene in the nuclei of MCF-7 cells.…”

Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas

“…This suggests that there is concomitant expression of basic FGF and FGF receptor in pancreatic ductal adenocarcinomas, which may allow for excessive autocrine growth stimulation. Furthermore, eight (25%) tumours had nuclear staining for basic FGF, supporting the concept of an intracellular stimulating effect like that of sis protein (Yamamoto et al, 1991;Nakanishi et al, 1992), i.e. the presence of basic FGF protein in the nucleus has raised the possibility of specific nuclear functions for this molecule in addition to signalling at the cell surface (Mason, 1994 Follow-up (months) studies suggesting the importance of contacts between tumour cells and fibroblasts (Tanaka et al, 1988;Coucke et al, 1992;Gartner et al, 1992).…”

Increased expression of a COOH‐truncated nucleophosmin resulting from alternative splicing is associated with cellular resistance to ionizing radiation in HeLa cells

“…FGF-2 has been implicated in transcription regulation. 33,34 In particular, FGF-2 is known to activate various transcription factors 35 and regulates the serum response factor (SRF) promoter. 36 However, it has also been demonstrated that FGF could regulate the alternative splicing of FGF receptor 2 and 3 (FGFR-2 or -3).…”