Multiple chromosomes carrying tumor suppressor activity for a uterine endometrial carcinoma cell line identified by microcell-mediated chromosome transfer.
Multiple chromosomes carrying tumor suppressor activity for a uterine endometrial carcinoma cell line identified by microcell-mediated chromosome transfer.
复制标题
通过微细胞介导的染色体转移鉴定出具有子宫内膜癌细胞系肿瘤抑制活性的多条染色体。
作者：
H. Yamada*;N. Wake;S. Fujimoto;Barrett Jc;M. Oshimura
通过微细胞融合，将正常细胞中的单个染色体导入到特定染色体上，可以将推定的肿瘤抑制基因定位到特定的染色体上。我们研究了高度恶性的人子宫内膜癌细胞系HHUA是否可以被一条正常染色体或多条染色体抑制。构建了含有用pSV 2-neo质粒DNA标记的不同人染色体的小鼠A9克隆文库。通过微细胞融合将1、6、9、11或19号染色体转移到HHUA肿瘤细胞系中，并检查微细胞杂交体在裸鼠中形成肿瘤的能力。染色体19的引入对细胞的致瘤性没有影响，而引入染色体1、6或9的微细胞杂交克隆的致瘤性完全被抑制。在引入11号染色体后，观察到一些但不是所有克隆的肿瘤发病率下降。引入1号染色体的非致瘤性微细胞杂交种不同于引入6、9或11号染色体的非致瘤性微细胞杂交种。一个很大的比例与1号染色体的杂交体衰老和/或细胞形态和转化的生长特性在体外表现出改变。转移其他染色体后，未观察到生长或形态学变化。这些结果可能表明，一个以上的染色体携带一个肿瘤抑制基因（S）的人子宫内膜癌细胞系，并支持假设，多个肿瘤抑制基因控制肿瘤发生表型的多步骤过程中的肿瘤发展。
Putative tumor suppressor genes can be mapped to specific chromosomes by the introduction of individual chromosomes derived from normal cells via microcell fusion. We have examined whether a highly malignant human uterine endometrial carcinoma cell line, HHUA, can be suppressed by only one normal chromosome or by multiple chromosomes. A library of mouse A9 clones containing different human chromosomes tagged with the pSV2-neo plasmid DNA were constructed. Transfer by microcell fusion of either chromosome 1, 6, 9, 11, or 19 into the HHUA tumor cell line was performed, and the abilities of the microcell hybrids to form tumors in nude mice were examined. The introduction of a chromosome 19 had no effect on the tumorigenicity of the cells, whereas microcell-hybrid clones with an introduced chromosome 1, 6 or 9 were completely suppressed for tumorigenicity. A decrease in tumor-take incidence in some but not all clones was observed following the introduction of a chromosome 11. The nontumorigenic microcell hybrids with an introduced chromosome 1 differed from the nontumorigenic microcell hybrids with an introduced chromosome 6, 9, or 11. A large percentage of hybrids with chromosome 1 senesced and/or showed alterations in cellular morphology and transformed growth properties in vitro. No growth or morphology alterations were observed following transfer of the other chromosomes. These results may indicate that more than one chromosome carries a tumor suppressor gene(s) for this human uterine endometrial carcinoma cell line and support the hypothesis that multiple tumor suppressor genes control the tumorigenic phenotype in the multistep process of neoplastic development.