Theile M, Hartmann S, Scherthan H, Arnold W, Deppert W, Frege R, Glaab F, Haensch W, Scherneck S
Arbeitsgruppe Tumorgenetik, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
Oncogene. 1995 Feb 2;10(3):439-47.
A number of candidate tumor suppressor genes located on the human chromosome 17 are thought to have a role to play in the development of breast cancer. In addition to the p53 gene on 17p13.1 and the BRCA1 gene mapped to 17q12-21, other chromosomal regions for tumor suppressor genes have been suggested to exist on 17p13.3 and both the central and the distal parts of 17q, although definitive functional proof of their involvement in breast cancer tumorigenesis is still lacking. In this report we show that microcell transfer of a human chromosome 17 into wild-type p53 breast cancer cells CAL51 results in loss of tumorigenicity and anchorage-independent growth, changes in cell morphology and a reduction of cell growth rates of the neo-selected microcell hybrids. In the hybrid cells, which express the p53 wild-type protein, only the p- and the distal parts of the q arm of donor chromosome 17 are transferred. Thus, our results provide functional evidence for the presence of one or more tumor suppressor gene(s) on chromosome 17, which are distinct from the p53 and the BRCA1 genes.
一些位于人类17号染色体上的候选肿瘤抑制基因被认为在乳腺癌的发展中发挥作用。除了位于17p13.1的p53基因和定位在17q12 - 21的BRCA1基因外,有人提出在17p13.3以及17q的中部和远端也存在其他肿瘤抑制基因的染色体区域,尽管仍缺乏它们参与乳腺癌肿瘤发生的确切功能证据。在本报告中,我们表明将人类17号染色体微细胞转移到野生型p53乳腺癌细胞CAL51中会导致致瘤性丧失和不依赖贴壁生长,细胞形态发生变化,并且新选择的微细胞杂种的细胞生长速率降低。在表达p53野生型蛋白的杂种细胞中,仅转移了供体17号染色体q臂的近端和远端部分。因此,我们的结果为17号染色体上存在一个或多个与p53和BRCA1基因不同的肿瘤抑制基因提供了功能证据。