Conditioned tumorigenicity of activated oncogenes.
Conditioned tumorigenicity of activated oncogenes.
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发表时间：
1986-07
期刊：
影响因子：
11.2
通讯作者：
G. Klein;E. Klein
中科院分区：
文献类型：
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作者：
G. Klein;E. Klein
病毒转导的癌基因（v-onc）具有有限的靶细胞谱。它们只转化表达它们的一小部分细胞类型。温度敏感（ts）突变体研究表明，其中一些突变体可能通过阻断成熟的特定步骤起作用。如果细胞可以绕过这个障碍，例如，通过暂时关闭对温度敏感的转化蛋白，那么在允许的温度下重新表达致癌基因产物可能无法恢复转化的表型。考虑到这些事实，再加上在正常细胞和恶性细胞融合产生的杂交细胞中有关转化表型逆转和致瘤性抑制的证据，就产生了“条件致瘤性”的概念。它指出，由结构或调节变化激活的特定癌基因的转化和/或致瘤作用仅限于每个易感谱系中特定且通常相当狭窄的分化或成熟窗口。类似的限制似乎适用于由染色体易位激活的癌基因。在伯基特淋巴瘤、小鼠浆细胞瘤和大鼠免疫细胞瘤中，c-myc基因与三个免疫球蛋白位点之一的常规并位就是一个很好的例子。携带myc的染色体可以在许多不同的地方断裂，在基因的内部、上游或下游，但不会在其编码外显子内断裂。这表明断裂是随机发生的，myc蛋白在选择性，即致瘤过程中起重要作用。如果是这样，其他癌基因应该同样可以转座到“Ig热点”，在肿瘤前靶细胞群的长系列细胞分裂中，这是BL和MPC的史前特征。在其他人类b细胞白血病和淋巴瘤中，也发现了其他易位（例如11、14和14、18），证实了这种情况确实可能发生，但仅在组织学上不同的肿瘤中发生。myc在BL和MPC中的独家参与必须与前体细胞的特定功能特征和myc蛋白的正常作用有关。最近的证据表明，myc基因在细胞进入一个被编程引导其进入静止Go状态的途径之前或当时被定期关闭。克隆扩增的b细胞被认为在抗原刺激减弱时变成静止记忆细胞。正常的、非易位的myc等位基因在BL和MPC中都有规律地关闭，这表明细胞已经遵循了myc下调的程序。（摘要删节为400字）
Virally transduced oncogenes (v-onc) have a restricted target cell spectrum. They transform only a small part of the cell types in which they are expressed. Temperature-sensitive (ts) mutant studies have shown that some of them may act by blocking specific steps of maturation. If the cell can bypass the block, e.g., by a temporary switch off of the temperature-sensitive transforming protein, reexpression of the oncogene product at the permissive temperature may be unable to restore the transformed phenotype. Consideration of these facts, together with evidence concerning the reversion of the transformed phenotype and the suppression of tumorigenicity in hybrids derived from the fusion of normal and malignant cells, leads to the concept of "conditioned tumorigenicity." It states that the transforming and/or tumorigenic effect of a given oncogene, activated by structural or by regulatory changes, is restricted to specific and often quite narrow differentiation or maturation windows within each susceptible lineage. A similar restriction seems to apply to oncogenes activated by chromosomal translocation. The regular juxtaposition of the c-myc gene to one of the three immunoglobulin loci in Burkitt's lymphoma, mouse plasmacytoma, and rat immunocytoma is a case in point. The myc-carrying chromosome can break at many different places, within, upstream, or downstream of the gene, but not within its coding exons. This suggests that the break occurs at random and the myc protein plays an essential role in the selective, i.e., tumorigenic process. If so, other oncogenes should be equally transposable to the "Ig hot spots" during the long series of cell divisions in the preneoplastic target cell population that characterizes the prehistory of both BL and MPC. In other human B-cell leukemias and lymphomas, other (e.g., 11;14 and 14;18) translocations have been found, confirming that this can actually occur, but only in histologically different neoplasms. The exclusive involvement of myc in BL and MPC must be relatable to the specific functional features of the precursor cells and to the normal role of the myc protein. Recent evidence indicates that the myc gene is regularly turned off before or at the time when the cell enters a pathway that is programmed to lead it towards a resting Go state. Clonally expanded B-cells are believed to turn into resting memory cells upon waning of the antigenic stimulus. The normal, nontranslocated myc allele is regularly switched off in both BL and MPC, indicating that the cell has already obeyed a program involving the down-regulation of myc.(ABSTRACT TRUNCATED AT 400 WORDS)