NONTUMORIGENIC SQUAMOUS-CELL CARCINOMA LINE CONVERTED TO TUMORIGENICITY WITH METHYL METHANESULFONATE WITHOUT ACTIVATION OF HRAS OR MYC
NONTUMORIGENIC SQUAMOUS-CELL CARCINOMA LINE CONVERTED TO TUMORIGENICITY WITH METHYL METHANESULFONATE WITHOUT ACTIVATION OF HRAS OR MYC
复制标题
DOI：
10.1073/pnas.87.4.1268
复制
发表时间：
1990-02-01
影响因子：
11.1
通讯作者：
TREWYN, RW
中科院分区：
文献类型：
--
作者：
MILO, GE;SHULER, C;TREWYN, RW
人类肿瘤群体的可塑性可以解释为什么许多致瘤人类细胞系在培养中生长时失去了这一特征。使用甲磺酸甲酯（MMS）将癌前鳞状细胞癌（SCC）细胞系SCC-83-01-82转化为恶性表型。MMS处理的SCC-83-01-82细胞（MMS-SCC-83-01-82）在3-5个月内在11只脾切除的BALB/c裸鼠中的5只中产生进行性生长的肿瘤。从其中一个小鼠肿瘤体外建立了命名为SCC-83-01-82 CA的细胞系，并连续传代。该SCC-83-01-82 CA细胞系具有侵袭性致瘤性。肿瘤。2.0与MMS-SCC-83-01-82细胞产生的肿瘤所需的3-5个月相反，通过原位杂交检查冷冻横截面显示，由MMS-SCC-83-01-82细胞产生的肿瘤的病灶区域表达MYC和HRAS mRNA。然而，到体内第三代，小鼠肿瘤中相应基因的表达水平检测不到。来自MMS-SCC-83-01-82细胞和随后衍生的肿瘤和细胞的RNA的印迹杂交分析没有表明MYC、HRAS或KRAS的任何一致的过表达。MYC和HRAS基因的限制性片段长度多态性分析均未发现MYC基因重排或扩增，也未发现HRAS第11或第12位密码子的点突变。这些数据表明，MYC和HRAS的改变并不直接参与SCC-83-01-82细胞系的初始转化或MMS诱导的致瘤性转化。MMS转化的癌前病变SCC-83-01-82细胞再分离后，致瘤性的持续性在MMS治疗后并没有立即消失。
Plasticity of human tumor populations could account for the reason why many tumorigenic human cell lines lose this feature when grown in culture. Methyl methanesulfonate (MMS) was used to convert premalignant squamous cell carcinoma (SCC) cell line SCC-83-01-82 to a malignant phenotype. the MMS-treated SCC-83-01-82 cells (MMS-SCC-83-01-82) produced progressively growing tumors in 5 of 11 splenectomized BALB/c nude mice within 3-5 months. A cell line, designated SCC-83-01-82 CA, was established in vitro from one of the mouse tumors and was repassaged successively. This SCC-83-01-82 CA cells line was aggressively tumorigenic. A tumor .gtoreq. 2.0 cm in size was present within a month, as opposed to the 3-5 months required for the tumors produced by the MMS-SCC-83-01-82 cells. Examination of frozen cross sections by in situ hybridization revealed that focal areas of the tumor produced by the MMS-SCC-83-01-82 cells expressed MYC and HRAS mRNA. However, by the third passage in vivo, the level of expression of the corresponding genes in the mouse tumors were undetectable. Blot-hybridization analysis of the RNA from the MMS-SCC-83-01-82 cells and the subsequently derived tumors and cells did not indicate any consistent overexpression of MYC, HRAS, or KRAS. Restriction fragment length polymorphism analysis of both MYC and HRAS genes revealed neither rearrangement nor amplification of MYC nor point mutation in the 11th or 12th codon of HRAS. The data suggest that alterations in MYC and HRAS were not directly involved in either the initial transformation or MMS-induced tumorigenic conversion of the SCC-83-01-82 cell line. Persistence of tumorigenicity after reisolation of the MMS-converted premalignant SCC-83-01-82 cells did not disappear immediately following the treatment with MMS.