Delgado M D, Hallier M, Meneceur P, Tavitian A, Moreau-Gachelin F
INSERM U248, Faculté de Médecine, Paris, France.
Oncogene. 1994 Jun;9(6):1723-7.
The spi-1 proto-oncogene encodes the transcription factor PU.1 which is normally expressed in all hematopoietic cell lineages except in T cell lines. During the murine acute erythroleukemia induced by the Friend retrovirus, SFFV, spi-1 deregulation by insertional mutagenesis results in the overexpression of Spi-1/PU.1 in the malignant proerythroblastic cell. To assess the Spi-1 role in the proliferation and the differentiation arrest of the Friend tumor cells we inhibited spi-1 gene expression in two Friend cell lines by using antisense oligodeoxyribonucleotides. Proliferation and cloning efficiency of both cell lines were significantly inhibited by spi1 antisense. This antiproliferative effect was not related to an apparent maturation of erythroleukemic cells demonstrating that repression of spi-1 expression is not sufficient per se to restore the ability of the proerythroblastic cells to spontaneously differentiate in mature erythroblasts. These data suggest that the spi-1 gene would be involved in the Friend leukemic process by promoting the proerythroblast to proliferate.
原癌基因spi-1编码转录因子PU.1，该因子通常在除T细胞系之外的所有造血细胞谱系中表达。在由弗氏病毒SFFV诱导的小鼠急性红白血病中，通过插入诱变使spi-1失调，导致恶性原红细胞中Spi-1/PU.1过表达。为了评估Spi-1在弗氏肿瘤细胞增殖和分化停滞中的作用，我们通过使用反义寡脱氧核糖核苷酸抑制了两个弗氏细胞系中的spi-1基因表达。spi1反义显著抑制了两个细胞系的增殖和克隆效率。这种抗增殖作用与红白血病细胞的明显成熟无关，这表明抑制spi-1表达本身不足以恢复原红细胞自发分化为成熟红细胞的能力。这些数据表明，spi-1基因可能通过促进原红细胞增殖而参与弗氏白血病进程。
