期刊
CANCER SCIENCE
卷 100, 期 1, 页码 47-53出版社
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1349-7006.2008.00991.x
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类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [16209013]
- Practical Application Research from the Japan Science and Technology Agency [H14-2]
- Ministry of Health, Labor and Welfare [H17-Gann-Rinsyo-006]
- Japan Society for the Promotion of Science [02568]
- Northern Advancement Center for Science and Technology [H18-Waka-075]
- Uehara Memorial Foundation [H19-Kenkyu-Syorei]
- Grants-in-Aid for Scientific Research [21590401] Funding Source: KAKEN
Papillomavirus binding factor (PBF) was first identified as a transcription factor regulating the promoter activity of human papillomavirus. We previously demonstrated that PBF is an osteosarcoma-associated antigen and 92% of osteosarcoma tissues express PBF in the nucleus. Moreover, PBF-positive osteosarcoma has a significantly poorer prognosis than that with negative expression of PBF. In the present study, we assessed the biological role of PBF in cell survival. Overexpression of PBF induced cell death-mediated lactate dehydrase (LDH) release from 293EBNA cells. Cleaved poly(ADP-ribose) polymerase and active caspase-3 were also detected. However, PBF-induced apoptosis did not affect caspase-9 activity. Next, to identify the apoptosis regulator of PBF, we screened a cDNA library constructed from mRNA of the osteosarcoma cell line OS2000 using a yeast two-hybrid system and isolated Scythe/BAT3. Scythe/BAT3 mRNA was detected in 56% of osteosarcoma tissues and ubiquitously in various normal tissues. Although Scythe/BAT3 was localized to the cytoplasm in normal tissue, it was localized to the nucleus in osteosarcoma tissue. PBF and Scythe/BAT3 also colocalized to the cytoplasm in 293T cells and the nucleus in OS2000. Furthermore, overexpression of Scythe/BAT3 suppressed cell death events that resulted from overexpression of PBF in OS2000, but not in 293EBNA cells. Thus, our results support the ideas that: (i) PBF could induce apoptotic cell death via a caspase-9-independent pathway; (ii) the apoptosis regulator Scythe/BAT3 is a PBF-associated molecule acting as a nucleus-cytoplasm shuttling protein; and (iii) colocalization of PBF and Scythe/BAT3 in the nucleus might be an important factor for survival of osteosarcoma cells. (Cancer Sci 2009; 100: 47-53).
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