Hypomethylation of ras oncogenes in chemically induced and spontaneous B6C3F1 mouse liver tumors.
Hypomethylation of ras oncogenes in chemically induced and spontaneous B6C3F1 mouse liver tumors.
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化学诱导和自发 B6C3F1 小鼠肝脏肿瘤中 ras 癌基因的低甲基化。
DOI：
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
J. Goodman
中科院分区：
文献类型：
--
作者：
R. L. Vorce;J. Goodman
雄性杂交B6 C3 F1小鼠表现出30%的自发性肝癌发生率，并且该品系的雄性和雌性均对肝肿瘤的化学诱导敏感。Ha-ras、Ki-ras和myc癌基因与多种实体瘤有关。具体地说，Ha-和，不太常见的Ki-ras已被报道在B6 C3 F1小鼠肝肿瘤中被激活，并且这种激活的癌基因经常包含特定的点突变。鉴于某些癌基因的转化能力与基因产物的水平直接相关，我们假设Ha-ras、Ki-ras和myc的转录控制在B6 C3 F1小鼠肝肿瘤中受到损害。基因表达和低甲基化之间存在正相关。因此，这些基因的甲基化状态进行了检查，在自发性肝肿瘤和肿瘤诱导的两种不同的肝癌：苯巴比妥和氯仿。Ha-ras被发现是低甲基化在所有的肿瘤检查，而Ki-ras有时低甲基化，这种低甲基化可能发挥作用，在促进阶段的致癌作用。myc的甲基化状态没有改变，尽管该基因似乎在肿瘤中扩增。这些结果表明，这些癌基因在B6 C3 F1小鼠肝肿瘤中被激活的机制的一个组成部分涉及失去严格的表达控制，通过低甲基化的ras癌基因，并可能，扩增myc。这些结果支持了不同种类的致癌物诱导的肿瘤或自发产生的肿瘤在肿瘤发生过程中具有共同的癌基因激活的生化途径的论断。
The male hybrid B6C3F1 mouse exhibits a 30% spontaneous hepatoma incidence, and both males and females of this strain are sensitive to chemical induction of liver tumors. The Ha-ras, Ki-ras, and myc oncogenes have been implicated in a variety of solid tumors. Specifically, Ha- and, less frequently Ki-ras have been reported to be activated in B6C3F1 mouse liver tumors, and such activated oncogenes frequently contain a particular point mutation. In light of indications that the transforming capacity of some oncogenes is directly related to the level of the gene product, we hypothesized that transcriptional control of Ha-ras, Ki-ras, and myc is compromised in B6C3F1 mouse liver tumors. A positive correlation has been established between gene expression and hypomethylation. Therefore, the methylation states of these genes were examined in spontaneous liver tumors and in tumors induced by two diverse hepatocarcinogens: phenobarbital and chloroform. Ha-ras was found to be hypomethylated in all tumors examined, whereas Ki-ras was sometimes hypomethylated; such hypomethylation might play a role in the promotion stage of carcinogenesis. The methylation state of myc was unaltered, although this gene appeared to be amplified in tumors. These results suggest that a component of the mechanism by which these oncogenes are activated in B6C3F1 mouse liver tumors involves loss of stringent control of expression, via hypomethylation of the ras oncogenes and, possibly, amplification of myc. These results support the assertion that tumors induced by different classes of carcinogens or arising spontaneously share common biochemical pathways of oncogene activation during tumorigenesis.
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一种检测和表征转录基因点突变的方法：人类肿瘤细胞中突变 c-Ki-ras 等位基因的扩增和过度表达。
DOI：
10.1073/pnas.82.22.7575
发表时间：
1985
影响因子：
11.1
作者：
Winter,E;Yamamoto,F;Almoguera,C;Perucho,M
通讯作者：
Perucho,M
DOI：
10.1073/pnas.83.16.5825
发表时间：
1986-08
影响因子：
11.1
作者：
R. Wiseman;S. Stowers;E. Miller;M. Anderson;J. Miller
通讯作者：
R. Wiseman;S. Stowers;E. Miller;M. Anderson;J. Miller
Ha-ras 表达升高是 SENCAR 小鼠两阶段皮肤癌发生的早期事件。
影响因子：
4.7
作者：
Pelling,JC;Ernst,SM;Strawhecker,JM;Johnson,JA;Nairn,RS;Slaga,TJ
通讯作者：
Slaga,TJ
大鼠肝癌和肝癌发生过程中癌基因的表达。
影响因子：
9.7
作者：
Cote,GJ;Lastra,BA;Cook,JR;Huang,DP;Chiu,JF
通讯作者：
Chiu,JF
体外顺式调节元件的 DNA 胞嘧啶甲基化调节体内 c-Ha-ras 启动子活性。
影响因子：
14.9
作者：
Rachal,MJ;Yoo,H;Becker,FF;Lapeyre,JN
通讯作者：
Lapeyre,JN