Zinyk D L, McGonnigal B G, Dearolf C R
Developmental Genetics Group, Dana Farber Cancer Institute, Boston, Massachusetts.
Nat Genet. 1993 Jun;4(2):195-201. doi: 10.1038/ng0693-195.
The human nm23-H1 gene is a suppressor of solid tumour metastasis in some types of cancer. It is known that nm23 genes encode nucleoside diphosphate kinase polypeptides, but the regulatory pathways involving Nm23 are unclear. One approach to understanding nm23 function is to identify loci which interact with nm23. The Drosophila awd gene, a homologue of nm23, provides a model system for this genetic analysis. We report that the dominant awdK-pn allele suppresses haematopoietic defects associated with the Tum-l oncogene. Premature differentiation and aggregation of Tum-l blood cells is reduced by awdK-pn, resulting in an increased survival of Tum-l hemizygotes. Tum-l lethality is also suppressed by pn mutations, indicating the existence of a haematopoietic regulatory pathway involving the Tum-l, AwdK-pn and Pn proteins.
人类nm23-H1基因在某些类型的癌症中是实体瘤转移的抑制因子。已知nm23基因编码核苷二磷酸激酶多肽,但涉及Nm23的调控途径尚不清楚。理解nm23功能的一种方法是鉴定与nm23相互作用的基因座。果蝇awd基因是nm23的同源物,为这种遗传分析提供了一个模型系统。我们报告说,显性awdK-pn等位基因抑制与Tum-l癌基因相关的造血缺陷。awdK-pn减少了Tum-l血细胞的过早分化和聚集,导致Tum-l半合子的存活率增加。pn突变也抑制了Tum-l的致死性,表明存在一条涉及Tum-l、AwdK-pn和Pn蛋白的造血调控途径。