Summary
Fibroblast growth factor‐2 (FGF‐2) gene expression is reported to be spatially and temporally regulated in the process of development, normal growth, and wound healing. We postulated that its constitutive expression in human malignant astrocytoma cells is due to loss of function of the regulatory mechanism of FGF‐2 gene expression. Here, we report the characterization of a unique element in the FGF‐2 gene promoter. We investigated the transcriptional regulation of the FGF‐2 gene in a human malignant astrocytoma (U87MG) and a human hepatocellular carcinoma (HepG2) cell line. We found that a dyad symmetry element (DSE) in the FGF‐2 gene promoter exhibited different promoter activities; in HepG2 cells it did, while in U87MG cells it did not, exhibit repressive activity. Examination of the relative promoter activities of the DSE in a thymidine kinase promoter revealed it exerted different activities, just as it did in the 2 cell lines studied.
Gel shift assay demonstrated that 2 proteins bound to the DSE in nuclear extracts from HepG2 cells and that one protein was missing in nuclear extracts from U87MG cells. These results suggest that the DSE has a crucial role as a transcriptional regulatory element of FGF‐2 gene expression.
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Abraham JA, Mergia A, Whang JL, Tumolo A, Friedman J, Hjerrild KA, Gospodarowicz D, Fiddes JC Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factorScience 233: 545–548, 1986
Hanahan D, Folkman J, Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86: 353–364, 1996
Baird A Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factorsCurr Opin Neurobiol 4: 78–86, 1994
Takahashi JA, Mori H, Fukumoto M, Igarashi K, Jaye M, Oda Y, Kikuchi H, Hatanaka M Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissuesProc Natl Acad Sci USA 87: 5710–5714, 1990
Zagzag D, Miller DC, Sato Y, Rifkin DB, Burstein DE Immunohistochemical localization of basic fibroblast growth factor in astrocytomasCancer Res 50: 7393–7398, 1990
Cohn MJ, Izpisua-Belmonte JC, Abud H, Heath JK, Tickle C Fibroblast growth factors induce additional limb development from the flank of chick embryosCell 80: 739–746, 1995
Cotman CW, Gomez-Pinilla F, Basic fibroblast growth factor in the mature brain and its possible role in Alzheimer’s diseaseAnn NY Acad Sci 638: 221–231, 1991
Tooyama I, Kremer HPH, Hayden MR, Kimura H, McGeer EG, McGree PL Acidic and basic fibroblast growth factor-like immunoreactivity in the striatum and midbrain in Huntington’s diseaseBrain Res 610: 1–7, 1993
Biesiada E, Razandi M, Levin ER, Egr-1 activates basic fibroblast growth factor transcription. Mechanistic implications for astrocyte proliferationJ Biol Chem 271: 18576–18581, 1996
Care A, Silvani A, Meccia E, Mattia G, Stoppacciaro A, Parmiani G, Peschle C, Clombo MP HOXB7 constitutively activates basic fibroblast growth factor in melanomasMol Cell Biol 16: 4842–4851, 1996
Moffett J, Kratz E, Florkiewicz R, Stachowiak MK Promoter regions involved in density-dependent regulation of basic fibroblast growth factor gene expression in human astrocytic cellsProc Natl Acad Sci USA 93: 2470–2475, 1996
Stachowiak MK, Moffett J, Joy A, Puchaca E, Florkiewicz R, Stachowiak EK Regulation of bFGF gene expression and subcellular distribution of bFGF protein in adrenal medullary cellsJ Cell Biol 127: 203–223, 1994
Ueba T, Nosaka T, Takahashi JA, Shibatta F, Florkiewicz RZ, Vogelstein B, Oda Y, Kikuchi H Transcriptional regulation of basic fibroblast growth factor gene by p53 in human glioblastoma and hepatocellular carcinoma cellsProc Natl Acad Sci USA 91: 9009–9013, 1994
Wang D, Mayo MW, Baldwin AS Jr, Basic fibroblast growth factor transcriptional autoregulation requires EGR-1Oncogene 14: 2291–2299, 1997
Shibata F, Baird A, Florkiewicz RZ, Functional characterization of the human basic fibroblast growth factor gene promoterGrowth Factors 4: 277–287, 1991
Ueba T, Kaspar B, Zhao X, Gage FH Repression of human fibroblast growth factor 2 by a novel transcription factorJ Biol Chem 274: 10382–10387, 1999
Moffett J, Kratz E, Myers J, et al., Transcriptional regulation of fibroblast growth factor-2 expression in human astrocytes: implications for cell plasticityMol Biol Cell 9: 2269–2285, 1998
Liu E, Weissman B, Oncogenes and tumor suppressor genes Cancer Treat Res63: 1–13, 1992
Johnson PF, McKnight S, Eukaryotic transcriptional regulatory proteins Ann Rev Biochem 58: 799–839, 1989
Chen Y, Gill GN, A heterodimeric nuclear protein complex binds two palindromic sequences in the proximal enhancer of the human erbB-2 geneJ Biol Chem 271: 5183–5188, 1996
Tabuchi K, Fukuyama K, Mineta T, Oh-Uchida M, Hori K Altered structure and expression of the p53 gene in human neuroepithelial tumorsNeurol Med-Chir 32: 725–732, 1992
Bressac B, Galvin KM, Liang TJ, Isselbacher KJ, Wands JR, Ozturk M Abnormal structure and expression of p53 gene in human hepatocellular carcinomaProc Natl Acad Sci USA 87: 1973–1977, 1990
Luckow B, Schutz G, CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elementsNucleic Acids Res 15: 5490, 1991
Faller DV, Andrews NC, A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cellsNucleic Acids Res 19: 2499, 1991
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We thank Ms. Ursula Petralia for editing our manuscript. This work was supported by the Grant-in-aid from the Ministry of Education and Science to TU and HN.
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Ueba, T., Mori, H., Takahashi, J.A. et al. A dyad symmetry element in the fibroblast growth factor-2 gene promoter with different levels of activity in astrocytoma and hepatocelluar carcinoma cell lines. J Neurooncol 78, 107–111 (2006). https://doi.org/10.1007/s11060-005-9063-3
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DOI: https://doi.org/10.1007/s11060-005-9063-3