Mally M I, Vogt M, Swift S E, Haas M
Virology. 1985 Jul 15;144(1):115-26. doi: 10.1016/0042-6822(85)90310-1.
The differential expression of a series of proto-oncogenes has been examined in a group of cultured murine T-cell lymphomas that were induced following virus inoculation into, or X irradiation of, C57BL/6 mice. Two classes of T lymphoma cell lines were studied: growth factor-dependent (autocrine) cells, and growth factor-independent T lymphoma cells. Cell lines that were established from X-irradiation-induced T lymphomas were growth factor dependent, whereas T lymphoma lines grown from virus-induced tumors were generally growth factor independent. Of 18 cellular proto-oncogenes studied, five (c-myc, c-myb, c-abl, c-rasHa, c-rasKi) were consistently expressed in all cell lines tested. Thirteen other proto-oncogenes (c-mos, c-sis, c-rel, c-yes, c-fes3, c-fes4, c-fos, c-fms, c-src, c-erbA, c-erbB, int-1, Pim-1) were not expressed in any of the T lymphoma cells tested. Concanavalin A-stimulated spleen cells, representative of replicating T cells, expressed c-myc, c-abl, and Pim-1, suggesting that the products of these proto-oncogenes are involved in T-cell proliferation. The results indicate no qualitative differences (albeit some quantitative differences) in proto-oncogene expression between the growth factor-dependent and growth factor-independent cells. This suggests that expression of the five proto-oncogenes is in itself not sufficient to induce the progression of the growth factor-dependent cells to their fully growth factor-independent counterparts. Changes in the regulation of one or more of the five active proto-oncogenes, i.e., from an inducible to a constitutive state, and/or additional changes in the expression of other cellular genes may be required to induce the transformation of neoplastic T cells from growth factor dependence to growth factor independence.
在一组培养的小鼠T细胞淋巴瘤中,研究了一系列原癌基因的差异表达。这些淋巴瘤是通过将病毒接种到C57BL/6小鼠体内或对其进行X射线照射诱导产生的。研究了两类T淋巴瘤细胞系:生长因子依赖性(自分泌)细胞和生长因子非依赖性T淋巴瘤细胞。由X射线照射诱导的T淋巴瘤建立的细胞系是生长因子依赖性的,而由病毒诱导的肿瘤产生的T淋巴瘤细胞系通常是生长因子非依赖性的。在所研究的18种细胞原癌基因中,有5种(c-myc、c-myb、c-abl、c-rasHa、c-rasKi)在所有测试的细胞系中均持续表达。其他13种原癌基因(c-mos、c-sis、c-rel、c-yes、c-fes3、c-fes4、c-fos、c-fms、c-src、c-erbA、c-erbB、int-1、Pim-1)在任何测试的T淋巴瘤细胞中均未表达。作为复制T细胞代表的刀豆球蛋白A刺激的脾细胞表达c-myc、c-abl和Pim-1,表明这些原癌基因的产物参与T细胞增殖。结果表明,生长因子依赖性细胞和生长因子非依赖性细胞之间在原癌基因表达上没有质的差异(尽管有一些量的差异)。这表明这5种原癌基因的表达本身不足以诱导生长因子依赖性细胞发展为完全生长因子非依赖性细胞。可能需要5种活跃原癌基因中的一种或多种调控发生变化,即从可诱导状态转变为组成型状态,和/或其他细胞基因表达发生额外变化,才能诱导肿瘤性T细胞从生长因子依赖性转变为生长因子非依赖性。