Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1:: A possible mechanism of breast carcinogenesis
Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1:: A possible mechanism of breast carcinogenesis
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DOI：
10.1073/pnas.95.21.12608
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发表时间：
1998-10-13
影响因子：
11.1
通讯作者：
Pardee, AB
中科院分区：
文献类型：
--
作者：
Ford, HL;Kabingu, EN;Pardee, AB
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，它是一个新的同源盒基因亚家族中近期发现的成员。HSIX1在S期开始时不表达，在S期末期表达增加。由于其表达模式暗示在S期之后起作用，我们研究了HSIX1在G₂细胞周期检查点中的作用。在MCF7细胞中过表达HSIX1会消除对X射线照射的G₂细胞周期检查点。HSIX1在正常乳腺组织中不表达或表达很低，但在44%的原发性乳腺癌和90%的转移性病变中高表达。此外，HSIX1在多种癌细胞系中表达，表明其在多种肿瘤类型中具有重要功能。这些数据支持同源盒基因在肿瘤发生/肿瘤进展中的作用，可能是通过一种细胞周期功能。
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 Gz cell cycle checkpoint. Overexpression of HSIX1 in MCF7 cells abrogated the G(2) 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.