ABROGATION OF THE G(2) CELL-CYCLE CHECKPOINT ASSOCIATED WITH OVEREXPRESSION OF HSIX1 - A POSSIBLE MECHANISM OF BREAST CARCINOGENESIS

While conducting a search for cell cycle-regulated genes in human mamm ary 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 ef fect 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 o f cancer cell lines, suggesting an important function in multiple tumo r types. These data support the role for homeobox genes in tumorigenes is/tumor progression, possibly through a cell cycle function.