Suppression of tumorigenicity in the human prostate cancer cell line M12 via microcell-mediated restoration of chromosome 19.
Suppression of tumorigenicity in the human prostate cancer cell line M12 via microcell-mediated restoration of chromosome 19.
复制标题
通过微细胞介导的 19 号染色体修复来抑制人前列腺癌细胞系 M12 的致瘤性。
DOI：
10.1002/gcc.1128
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Ware,JL
中科院分区：
文献类型：
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作者：
Astbury,C;Jackson-Cook,CK;Culp,SH;Paisley,TE;Ware,JL
以前，我们用SV40大T抗原(SV40TAg)使未转化的人前列腺上皮细胞永生化，并从永生化的细胞系中衍生出越来越具侵袭性的亚系。在致瘤亚系向转移能力发展的过程中，伴随着16号和19号染色体之间形成的不平衡易位，导致19p和近端19q的丢失。为了测试致瘤和/或转移表型是否与这种基因改变有因果关系，我们通过微细胞介导的转移将新标记的人19号染色体恢复到M12细胞，并评估它们的生长。在体外，得到的杂交细胞在单层培养中生长较慢，并且与M12neo对照相比，非锚定生长显著降低。在体内，皮下注射对照M12neo细胞的所有小鼠(13/13)在9-15天后都出现了肿瘤。相比之下，9/15的小鼠注射了微细胞转移的19号染色体杂交细胞后未能形成肿瘤，其中6/15的小鼠在120天后产生了非常小的肿瘤。对这六种肿瘤中的三种的分析显示了一致的、新的染色体变化。此外，在其中一个肿瘤中，发现40%的细胞丢失了19号染色体。在前列腺内注射杂交细胞后，只有2/7的小鼠出现了微小肿瘤，没有转移。这些数据表明，19号染色体上存在一个或多个基因，该基因具有抑制生长的功能。©2001 Wiley-Liss公司
Previously we immortalized human, nontransformed prostate epithelial cells with SV40 large T‐antigen (SV40TAg) and derived increasingly aggressive sublines from the immortalized line. The progression of the tumorigenic sublines to metastatic capacity was accompanied by the formation of an unbalanced translocation between chromosomes 16 and 19, resulting in loss of 19p and proximal 19q. To test whether the tumorigenic and/or metastatic phenotype was causally related to this genetic alteration, we restored a neo‐tagged human chromosome 19 to M12 cells by microcell‐mediated transfer and assessed their growth. In vitro, the resultant hybrids grew more slowly in monolayer culture and showed a significant reduction in anchorage‐independent growth as compared to M12neo controls. In vivo, all mice (13/13) injected subcutaneously (SC) with control M12neo cells developed tumors after 9–15 days. In contrast, 9/15 mice injected SC with microcell‐transferred chromosome 19 hybrid cells failed to form tumors, with 6/15 producing very small tumors after 120 days. Analysis of three of these six tumors showed consistent, new chromosomal changes. Furthermore, in one of the tumors, loss of a chromosome 19 was noted in 40% of the cells. After intraprostatic injections of the hybrid cells, only 2/7 mice developed microscopic tumors, with no metastases. These data suggest the presence of a gene or genes on chromosome 19 that function to suppress growth. © 2001 Wiley‐Liss, Inc.