Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression.
Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression.
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恶性肿瘤进展过程中病毒转化的 BALB/c 3T3 细胞中 Kirsten ras 癌基因的扩增和重排。
DOI：
10.1073/pnas.84.15.5143
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发表时间：
1987
影响因子：
11.1
通讯作者：
Culp,LA
中科院分区：
文献类型：
--
作者：
Radinsky,R;Kraemer,PM;Raines,MA;Kung,HJ;Culp,LA
利用含有复制缺陷前病毒的Kirsten小鼠肉瘤病毒转化的BALB/c 3T3细胞，对恶性肿瘤进展过程中细胞和病毒Kirsten ras基因(分别为c-ki-ras和v-ki-ras)进行了分析。通过4种不同途径注射入裸鼠体内，分离原发肿瘤和继发性肺转移瘤，适应体外生长，分析两种基因的DNA水平和mRNA表达，并与最初注射的转化细胞和未转化的3T3细胞进行比较。所有肿瘤(原发或继发性)的v-ki-ras基因均被扩增，v-ki-ras基因的表达显著高于原始转化细胞群。每五个肺转移中就有两个来自静脉注射。和足垫注射途径，观察Ki-ras DNA序列重排。来自S.C.的微转移。注射途径未显示这些改变。将具有重排的Foot Pad肺肿瘤细胞注射到第二组动物体内，导致多发性肺转移，甚至进一步的重排与更有效的肺定植/生长能力相关(8只动物中有5只在注射后20天内出现明显的肺部肿瘤)。然而，静脉注射的再注射。KI-ras基因重排的肺肿瘤在注射后40d以上分离的肺微灶肿瘤没有进一步的重排。这些数据提示(I)v-ki-ras基因扩增和表达升高在肿瘤形成中的意义，(Ii)这种扩增与更有效的肿瘤进展的相关性，以及(Iii)具有Ki-ras DNA序列增加的细胞在显性肺肿瘤形成中的选择性优势。
Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) during malignant tumor progression were performed by using Kirsten murine sarcoma virus-transformed BALB/c 3T3 cells that harbor a replication-defective provirus. After injection into athymic nude mice by four different routes, primary tumors and secondary lung metastases were isolated, adapted to in vitro growth, and analyzed for DNA levels and mRNA expression of both genes for comparison with the originally injected transformed cells and untransformed 3T3 cells. For all tumors (primary or secondary), the v-Ki-ras gene was amplified and v-Ki-ras mRNA expression was highly elevated above that observed in the original transformed cell population. In two of five lung metastases from the i.v. and footpad injection routes, rearranged Ki-ras DNA sequences were observed. Micrometastases from the s.c. route of injection did not display these alterations. Injection of footpad lung tumor cells with rearrangements into a second group of animals led to multiple lung metastases with even further rearrangements correlating with more effective lung colonization/growth ability (overt lung tumors in five of eight animals less than 20 days after injection). However, reinjection of an i.v. lung tumor with rearranged Ki-ras led to no further rearrangements in the lung microfoci tumors isolated greater than 40 days after injection. These data suggest (i) the significance of amplification and elevated expression of v-Ki-ras in tumor formation, (ii) correlation of this amplification with more effective tumor progression, and (iii) the selective advantage that cells with Ki-ras DNA sequence additions have in the formation of overt lung tumors.