title: 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.
abstract: 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.
authors.affiliation: Department of Reproductive Medicine, First Affiliated Hospital, Xi'an Jiaotong University of Medical School, Xi'an, The People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Yang
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Zheng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology
chemical_list: C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D063150:Polycomb Repressive Complex 1