Robertson G P, Hufford A, Lugo T G
Division of Biomedical Sciences, University of California, Riverside, USA.
Cytogenet Cell Genet. 1997;79(1-2):53-9. doi: 10.1159/000134682.
Cytogenetic and molecular studies have implicated one or more tumor suppressor genes on the long arm of human chromosome 11 in the malignant progression of several human solid tumors, including malignant melanoma and carcinomas of the breast, cervix, ovary, and lung. Microcell-mediated chromosome transfer of an intact copy of chromosome 11 into tumor cell lines has provided additional evidence of tumor suppressor gene function in melanoma, breast cancer, and cervical cancer. However, sublocalization of the region(s) conferring the tumor suppressive effect has been difficult. To facilitate mapping of tumor suppressor gene(s) on chromosome 11, we have generated a panel of 25 mouse donor cell lines containing neo-tagged fragments of human chromosome 11q which can be transferred into cell lines to test for tumor suppressor activity. The chromosome fragments in these cell lines have been characterized by fluorescence in situ hybridization with probes to human DNA and to the centromere of chromosome 11, and also by analysis of microsatellite markers spanning chromosome 11. Finally, to demonstrate the usefulness of these cell lines as donors for microcell-mediated chromosome transfer, two fragments were transferred into the human melanoma cell line UACC 903. This panel of selectable subchromosomal fragments, derived from the long arm of human chromosome 11, will be useful for the regional localization of tumor suppressors and other genes by means of functional assays.
细胞遗传学和分子研究表明，人类11号染色体长臂上的一个或多个肿瘤抑制基因与几种人类实体瘤的恶性进展有关，包括恶性黑色素瘤以及乳腺癌、宫颈癌、卵巢癌和肺癌。将完整的11号染色体拷贝通过微细胞介导的染色体转移导入肿瘤细胞系，为黑色素瘤、乳腺癌和宫颈癌中的肿瘤抑制基因功能提供了额外证据。然而，确定赋予肿瘤抑制作用的区域的亚定位一直很困难。为了便于在11号染色体上定位肿瘤抑制基因，我们构建了一组由25个小鼠供体细胞系组成的文库，这些细胞系包含人11号染色体长臂的新标记片段，可将其导入细胞系以检测肿瘤抑制活性。这些细胞系中的染色体片段已通过用针对人类DNA和11号染色体着丝粒的探针进行荧光原位杂交，以及通过分析跨越11号染色体的微卫星标记进行了表征。最后，为了证明这些细胞系作为微细胞介导的染色体转移供体的实用性，将两个片段转移到了人类黑色素瘤细胞系UACC 903中。这组源自人类11号染色体长臂的可选择亚染色体片段，将通过功能测定法用于肿瘤抑制基因和其他基因的区域定位。
