Coexpression of B-lymphoma Moloney murine leukemia virus insertion region-1 and sex-determining region of Y chromosome-related high mobility group box-2 in cervical carcinogenesis.

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.

Xu R ，Yang WT ，Zheng PS 《-》

Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro.

Chang X ，Zhang J ，Huang C ，Pang X ，Luo Q ，Zhang H ，Zhang S ... -  《-》

Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes.

Xu R ，Chen L ，Yang WT 《-》

Overexpression of Bmi-1 in uterine cervical cancer: correlation with clinicopathology and prognosis.

Zhang X ，Wang CX ，Zhu CB ，Zhang J ，Kan SF ，Du LT ，Li W ，Wang LL ，Wang S ... -  《-》

Expression of Sox2 in human cervical carcinogenesis.

Sox2 is a key transcription factor for embryonic development and plays a critical role in determining the fate of stem cells. Recently, Sox2 has been detected in several human tumors, indicating a potential function in tumorigenesis. We initially reported remarkably increased nuclear Sox2 staining in cervical carcinomas compared with normal cervix (P < .05). Furthermore, Sox2 staining was detected in most tumorsphere cells isolated from fresh cervical cancer tissues but not among the differentiated tumorsphere cells. When Sox2 was stably expressed in cervical cancer cells (SiHa and HeLa), Sox2-overexpressing cells had increased proliferation, clonogenicity, and tumorigenicity in vitro and in vivo than control cells. These results suggest that Sox2 may participate in carcinogenesis of cervical carcinomas and may be a potential therapeutic target molecule for cervical cancers.

Ji J ，Zheng PS 《-》