Rimessi P, Gualandi F, Morelli C, Trabanelli C, Wu Q, Possati L, Montesi M, Barrett J C, Barbanti-Brodano G
Institute of Microbiology, School of Medicine, University of Ferrara, Italy.
Oncogene. 1994 Dec;9(12):3467-74.
The molecular pathogenesis of ovarian carcinoma involves altered expression of growth factors, activation of oncogenes and loss of tumor suppressor genes. Loss of heterozygosity on chromosomes 3p, 6q, 11p, 17 and 18q was reported as a significant alteration in ovarian cancer. However, no functional proof has been provided of tumor suppressor activity located in these chromosomal regions. We therefore introduced normal human chromosomes 3 and 11 into an ovarian carcinoma cell line by microcell mediated chromosome transfer. Transfer of chromosome 3 induced senescence and growth arrest as well as suppression of tumorigenicity. Tumors induced by chromosome 3 monochromosomic hybrids consistently lost three small regions on 3p, two of which located in 3p23-24.2 and one located in 3p21.1-21.2, suggesting that these chromosomal regions are important for suppression of tumorigenicity of ovarian carcinoma cells. Transfer of chromosome 11 reduced the in vitro growth properties of ovarian cancer cells but did not significantly affect tumorigenicity. These results provide functional evidence for chromosome 3 tumor suppressor activity in ovarian cancer and define the chromosomal regions on 3p involved in the pathogenesis of this tumor. This experimental system, based on functional effects, may be useful for further delimitation and isolation of critical regions on 3p involved in tumor suppression.
卵巢癌的分子发病机制涉及生长因子表达改变、癌基因激活和肿瘤抑制基因缺失。据报道，3p、6q、11p、17和18q染色体上的杂合性缺失是卵巢癌的一个重要改变。然而，尚未提供位于这些染色体区域的肿瘤抑制活性的功能证据。因此，我们通过微细胞介导的染色体转移将正常人类染色体3和11导入卵巢癌细胞系。染色体3的转移诱导了衰老和生长停滞以及肿瘤发生的抑制。由染色体3单染色体杂种诱导的肿瘤始终在3p上丢失三个小区域，其中两个位于3p23 - 24.2，一个位于3p21.1 - 21.2，这表明这些染色体区域对于抑制卵巢癌细胞的肿瘤发生很重要。染色体11的转移降低了卵巢癌细胞的体外生长特性，但对肿瘤发生没有显著影响。这些结果为卵巢癌中染色体3的肿瘤抑制活性提供了功能证据，并确定了参与该肿瘤发病机制的3p染色体区域。这个基于功能效应的实验系统可能有助于进一步界定和分离3p上参与肿瘤抑制的关键区域。
