Pampeno C L, Meruelo D
Department of Pathology, New York University Medical Center, New York 10016, USA.
Cell Growth Differ. 1996 Aug;7(8):1113-23.
Elucidation of the leukemogenic process induced by fractionated X-irradiation (FX) requires the identification of molecules that mediate the differentiation and regeneration of T cells. To isolate cDNA transcripts associated with FX-induced leukemia in C57BL/6 mice, a cDNA library was constructed from FX-induced thymoma mRNA and differentially screened with cDNA probes. A novel cDNA transcript, FX-induced transcript 1 (FXI-T1), showed strong differential mRNA expression in all C57BL/6 FX-induced thymomas examined when compared with normal thymus tissue. FXI-T1 was not universally expressed in proliferative or other neoplastic cells. Expression of FXI-T1 mRNA in untreated mouse organs was not restricted to the thymus; highest expression was observed in brain and skeletal muscle tissue. The translated FXI-T1 sequence encodes a basic, prolinerich protein that contains a RING-H2-finger motif. The COOH-terminal region of the putative FXI-T1 protein has sequence similarity with the COOH-terminal domain of the Drosophila deltex protein, a component of a signal pathway that functions during cell differentiation. The described observations suggest an association of FXI-T1 with FX-induced leukemogenesis. The study of FXI-T1 should contribute to an understanding of the processes of T-cell differentiation and regeneration in addition to leukemogenesis.
阐明分次X射线照射(FX)诱导的白血病发生过程需要鉴定介导T细胞分化和再生的分子。为了分离与C57BL/6小鼠中FX诱导的白血病相关的cDNA转录本,从FX诱导的胸腺瘤mRNA构建了一个cDNA文库,并用cDNA探针进行差异筛选。一种新的cDNA转录本,即FX诱导转录本1(FXI-T1),与正常胸腺组织相比,在所有检测的C57BL/6 FX诱导的胸腺瘤中显示出强烈的差异mRNA表达。FXI-T1在增殖性或其他肿瘤细胞中并非普遍表达。FXI-T1 mRNA在未处理的小鼠器官中的表达并不局限于胸腺;在脑和骨骼肌组织中观察到最高表达。翻译后的FXI-T1序列编码一种含有RING-H2手指基序的碱性、富含脯氨酸的蛋白质。推测的FXI-T1蛋白的COOH末端区域与果蝇deltex蛋白的COOH末端结构域具有序列相似性,deltex蛋白是细胞分化过程中起作用的信号通路的一个组成部分。上述观察结果表明FXI-T1与FX诱导的白血病发生有关。对FXI-T1的研究除了有助于了解白血病发生外,还应有助于理解T细胞分化和再生过程。