B-lymphoma Moloney murine leukemia virus insertion region-1 is an oncogene in various human tumors, and overexpression correlates with a poor clinical outcome. Sex-determining region of Y chromosome-related high mobility group box-2, coding for a critical transcription factor determining the fate of stem cells, was recently identified as an oncogene in human cervical carcinoma and other tumors. However, the roles of B-lymphoma Moloney murine leukemia virus insertion region-1 and sex-determining region of Y chromosome-related high mobility group box-2 in the pathogenesis of cervical carcinoma are poorly understood. We initially observed a more pronounced increase in B-lymphoma Moloney murine leukemia virus insertion region-1 protein expression in primary cervical carcinoma than in normal cervical tissues, and B-lymphoma Moloney murine leukemia virus insertion region-1 protein expression correlated significantly with sex-determining region of Y chromosome-related high mobility group box-2 protein expression, as seen by Western blotting (r = 0.75; P < .01). Furthermore, B-lymphoma Moloney murine leukemia virus insertion region-1 and sex-determining region of Y chromosome-related high mobility group box-2 both had higher expression in cervical carcinoma than in normal cervical tissue, and the amounts correlated with pathologic grade. Immunofluorescence analysis showed that B-lymphoma Moloney murine leukemia virus insertion region-1 colocalized in the nucleus with sex-determining region of Y chromosome-related high mobility group box-2 in both normal cervical tissue and cervical carcinoma. From the cervical carcinoma cell line SiHa, we isolated 2 clones, B-lymphoma Moloney murine leukemia virus insertion region-1(+)/sex-determining region of Y chromosome-related high mobility group box-2(+) (SiHa-3) and B-lymphoma Moloney murine leukemia virus insertion region-1(-)/sex-determining region of Y chromosome-related high mobility group box-2(-) (SiHa-2). The SiHa-3 cells grew better in vitro and formed tumors more readily in vivo than did SiHa-2. Knockout of sex-determining region of Y chromosome-related high mobility group box-2 inhibited cell growth in vitro with a block at G1/S. In contrast, knockout of B-lymphoma Moloney murine leukemia virus insertion region-1 did not affect either cell growth in vitro or the cell cycle. Interference with either B-lymphoma Moloney murine leukemia virus insertion region-1 or sex-determining region of Y chromosome-related high mobility group box-2 in SiHa-3 significantly inhibited tumorigenesis (P < .05). Coexpression of B-lymphoma Moloney murine leukemia virus insertion region-1 and sex-determining region of Y chromosome-related high mobility group box-2 may promote cervical carcinogenesis.
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