Tashiro Etsu, Minato Yusuke, Maruki Hiroko, Asagiri Masataka, Imoto Masaya
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Oncogene. 2003 Aug 28;22(36):5630-5. doi: 10.1038/sj.onc.1206636.
Fibroblast growth factors (FGF) and their receptors play an important role in cell proliferation, angiogenesis and embryonal development. In this study, we show that expression of the FGF receptor-2 (FGFR-2) protein is induced in the mid-to-late G1 phase of the cell cycle in serum-starved mouse NIH3T3 cells released from starvation. Transcription of mouse FGFR-2 was activated by E2F-1. Analysis of various mouse FGFR-2 promoter mutant constructs showed that a sequence located +57/+64 downstream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. The promoter activity of the mouse FGFR-2 gene is also positively regulated by E2F-2 and E2F-3, but not by E2F-4 and E2F-5. Moreover, the E2F-1-induced activation of mouse FGFR-2 gene transcription is suppressed by pRB. Taken together, the results demonstrate that FGFR-2 is a new class of targets for E2F, and expression of mouse FGFR-2 in mid-to-late G1 phase would be mediated, at least in part, by the activation of a pRB/E2F pathway.
成纤维细胞生长因子（FGF）及其受体在细胞增殖、血管生成和胚胎发育中发挥着重要作用。在本研究中，我们发现，在血清饥饿的小鼠NIH3T3细胞脱离饥饿状态后，细胞周期的G1期中后期会诱导FGF受体-2（FGFR-2）蛋白的表达。小鼠FGFR-2的转录由E2F-1激活。对各种小鼠FGFR-2启动子突变体构建体的分析表明，转录起始位点下游+57/+64处的一个与共有E2F反应序列相关的序列对于激活是必需的。小鼠FGFR-2基因的启动子活性也受到E2F-2和E2F-3的正向调节，但不受E2F-4和E2F-5的调节。此外，pRB抑制E2F-1诱导的小鼠FGFR-2基因转录激活。综上所述，结果表明FGFR-2是E2F的一类新靶点，小鼠FGFR-2在G1期中后期的表达至少部分由pRB/E2F途径的激活介导。
