Calabretta B, Kaczmarek L, Mars W, Ochoa D, Gibson C W, Hirschhorn R R, Baserga R
Proc Natl Acad Sci U S A. 1985 Jul;82(13):4463-7. doi: 10.1073/pnas.82.13.4463.
Three cDNA clones isolated from Syrian hamster cells (p4F1, p2F1, and p2A9) contain sequences that are preferentially expressed in the G1 phase of the cell cycle. The expression of these sequences was investigated in human peripheral blood cells from normal individuals and from patients with leukemia. The expression of p4F1 and p2F1 is clearly dependent on the cell cycle in peripheral blood mononuclear cells stimulated to proliferate with phytohemagglutinin; the p2A9 sequences cannot be clearly detected in human lymphocytes but are expressed in a cell-cycle-dependent manner in human diploid fibroblasts (WI-38). These genes also show different levels of expression in lymphoid and myeloid leukemias. The highest level of expression for p2A9 is found in patients with chronic myelogenous leukemia, and the lowest in patients with chronic lymphocytic leukemia. For p2F1 and p4F1, the highest levels of expression are found in chronic and acute myelogenous leukemia. At least two other cell-cycle genes are not expressed at detectable levels in human leukemias. These findings suggest that the activation of cell-division-cycle genes might contribute, like cellular oncogenes, to the phenotype of human malignancies and that, perhaps, new oncogenes could be found by identifying and isolating genes whose expression is dependent on the cell cycle.
从叙利亚仓鼠细胞中分离出的三个cDNA克隆（p4F1、p2F1和p2A9）包含在细胞周期G1期优先表达的序列。对正常个体和白血病患者外周血细胞中这些序列的表达进行了研究。在用植物血凝素刺激增殖的外周血单核细胞中，p4F1和p2F1的表达明显依赖于细胞周期；在人淋巴细胞中无法清楚检测到p2A9序列，但在人二倍体成纤维细胞（WI-38）中以细胞周期依赖性方式表达。这些基因在淋巴性白血病和髓性白血病中也表现出不同的表达水平。p2A9在慢性粒细胞白血病患者中表达水平最高，在慢性淋巴细胞白血病患者中最低。对于p2F1和p4F1，在慢性和急性髓性白血病中表达水平最高。至少另外两个细胞周期基因在人类白血病中未检测到表达。这些发现表明，细胞分裂周期基因的激活可能像细胞癌基因一样，对人类恶性肿瘤的表型有贡献，并且也许通过鉴定和分离其表达依赖于细胞周期的基因可以发现新的癌基因。
