Ford H L, Kabingu E N, Bump E A, Mutter G L, Pardee A B
Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12608-13. doi: 10.1073/pnas.95.21.12608.
While conducting a search for cell cycle-regulated genes in human mammary carcinoma cells, we identified HSIX1, a recently discovered member of a new homeobox gene subfamily. HSIX1 expression was absent at the onset of and increased toward the end of S phase. Since its expression pattern is suggestive of a role after S phase, we investigated the effect of HSIX1 in the G2 cell cycle checkpoint. Overexpression of HSIX1 in MCF7 cells abrogated the G2 cell cycle checkpoint in response to x-ray irradiation. HSIX1 expression was absent or very low in normal mammary tissue, but was high in 44% of primary breast cancers and 90% of metastatic lesions. In addition, HSIX1 was expressed in a variety of cancer cell lines, suggesting an important function in multiple tumor types. These data support the role for homeobox genes in tumorigenesis/tumor progression, possibly through a cell cycle function.
在对人乳腺癌细胞中细胞周期调控基因进行搜索时，我们鉴定出了HSIX1，它是一个新的同源框基因亚家族中最近发现的成员。HSIX1在S期开始时不存在，而在S期末期表达增加。由于其表达模式提示在S期之后发挥作用，我们研究了HSIX1在G2细胞周期检查点中的作用。MCF7细胞中HSIX1的过表达消除了对X射线照射的G2细胞周期检查点。HSIX1在正常乳腺组织中不存在或表达非常低，但在44%的原发性乳腺癌和90%的转移病灶中高表达。此外，HSIX1在多种癌细胞系中表达，提示其在多种肿瘤类型中具有重要功能。这些数据支持同源框基因在肿瘤发生/肿瘤进展中的作用，可能是通过细胞周期功能实现的。
