Menke A L, van Ham R C, Sonneveld E, Shvarts A, Stanbridge E J, Miyagawa K, van der Eb A J, Jochemsen A G
Laboratory for Molecular Carcinogenesis, Leiden University, The Netherlands.
Int J Cancer. 1995 Sep 27;63(1):76-85. doi: 10.1002/ijc.2910630115.
Human chromosome 11 was introduced into adenovirus-transformed baby rat kidney (BRK) cells by microcell-mediated chromosome transfer. The resulting microcell hybrids (MCHs) showed a reduced ability to form tumors upon s.c. injection into athymic mice. Further analysis, with the use of defined deletion chromosomes of 11p, indicated that the presence of region 11p13-p12 is necessary for the suppression of tumorigenicity. In contrast, the presence of region 11p15-14.1 appeared to increase the rate of tumor growth. Expression studies on the human Wilms' tumor I (WTI) and the insulin-like growth factor II (IGF-II) genes, which lie in regions 11p13 and 11p15, respectively, suggested the involvement of both genes in determining the degree of suppression of tumorigenicity. Finally, stable expression of a murine WTI protein in the adenovirus-transformed cells resulted in almost complete suppression of tumorigenicity, establishing the WTI protein as a tumor suppressor in this cell system.
通过微细胞介导的染色体转移将人类11号染色体导入腺病毒转化的新生大鼠肾（BRK）细胞。将所得的微细胞杂种（MCH）皮下注射到无胸腺小鼠体内后，其形成肿瘤的能力降低。使用11p的特定缺失染色体进行的进一步分析表明，11p13-p12区域的存在对于抑制致瘤性是必需的。相反，11p15-14.1区域的存在似乎增加了肿瘤生长速率。对分别位于11p13和11p15区域的人类肾母细胞瘤I（WTI）基因和胰岛素样生长因子II（IGF-II）基因的表达研究表明，这两个基因都参与了决定致瘤性抑制程度的过程。最后，腺病毒转化细胞中鼠WTI蛋白的稳定表达几乎完全抑制了致瘤性，确立了WTI蛋白在该细胞系统中作为肿瘤抑制因子的地位。
