AMPLIFICATION OF THE E2F1 TRANSCRIPTION FACTOR GENE IN THE HEL ERYTHROLEUKEMIA CELL-LINE
AMPLIFICATION OF THE E2F1 TRANSCRIPTION FACTOR GENE IN THE HEL ERYTHROLEUKEMIA CELL-LINE
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DOI：
10.1016/0888-7543(95)80118-6
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发表时间：
1995-01-01
期刊：
影响因子：
4.4
通讯作者：
LOOK, AT
中科院分区：
文献类型：
--
作者：
SAITO, M;HELIN, K;LOOK, AT
E2F转录因子在细胞增殖中起重要的调节作用，它介导一些基因的表达，这些基因的产物对于诱导静止细胞进入细胞周期并合成DNA是必不可少的。为了研究E2F在造血系统恶性肿瘤中可能的参与情况，我们分离了包含人E2F1基因的基因组克隆。然后我们利用荧光原位杂交将E2F1定位到人类20号染色体q11区，位于p107基因座的端粒侧，p107基因的产物与视网膜母细胞瘤基因产物（pRb）相关。这一发现与先前确定的E2F家族另外两个成员E2F2和E2F3分别位于1号染色体p36区和6号染色体q22区的染色体位置形成对比。尽管在14例具有20号染色体q11区结构异常的原发性急性白血病或骨髓增生异常综合征样本中未检测到E2F1的缺失或结构重排，但该基因在HEL红白血病细胞中发生扩增和过度表达，并且在几种已建立的人类白血病细胞系中易位到其他染色体。这项研究提供了涉及E2F转录因子家族成员基因扩增的首个证据。我们提出，红系祖细胞中E2F1的过度表达可能通过克服由肿瘤抑制蛋白（如pRb）介导的负性调节信号来刺激异常细胞增殖。（C）1995年学术出版社
The E2F transcription factor plays an important regulatory role in cell proliferation, mediating the expression of genes whose products are essential for inducing resting cells to enter the cell cycle and synthesize DNA. To investigate the possible involvement of E2F in hematopoietic malignancies, we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 20q11, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22 chromosomal locations previously assigned E2F2 and E2F3, two additional members of the E2F family. Although deletions or structural rearrangements of E2F1 were not detected in 14 primary acute leukemia or myelodysplasia samples with structural abnormalities of chromosome 20q11, the gene was amplified and overexpressed in HEL erythroleukemia cells and translocated to other chromosomes in several established human leukemia cell lines. This study provides the first evidence of gene amplification involving a member of the E2F family of transcription factors. We propose that E2F1 overexpression in erythroid progenitors may stimulate abnormal cell proliferation by overriding negative regulatory signals mediated by tumor suppressor proteins such as pRb. (C) 1995 Academic Press, Inc.