Oncoprotein BMI-1 induces the malignant transformation of HaCaT cells.
BMI-1 (B-cell-specific Moloney murine leukemia virus integration site 1), a novel oncogene, has attracted much attention in recent years for its involvement in the initiation of a variety of tumors. Recent evidence showed that BMI-1 was highly expressed in neoplastic skin lesions. However, whether dysregulated BMI-1 expression is causal for the transformation of skin cells remains unknown. In this study, we stably expressed BMI-1 in a human keratinocyte cell line, HaCaT. The expression of wild-type BMI-1 induced the malignant transformation of HaCaT cells in vitro. More importantly, we found that expression of BMI-1 promoted formation of squamous cell carcinomas in vivo. Furthermore, we showed that BMI-1 expression led to the downregulation of tumor suppressors, such as p16INK4a and p14ARF, cell adhesion molecules, such as E-Cadherin, and differentiation related factor, such as KRT6. Therefore, our findings demonstrated that dysregulated BMI-1 could indeed lead to keratinocytes transformation and tumorigenesis, potentially through promoting cell cycle progression and increasing cell mobility.
Wang
Qian
Q
Department of Cell Biology, Second Military Medical University, Shanghai 200433, PR China.
Li
Wen-Lin
WL
You
Pu
P
Su
Juan
J
Zhu
Ming-Hua
MH
Xie
Dong-Fu
DF
Zhu
Hai-Yin
HY
He
Zhi-Ying
ZY
Li
Jian-Xiu
JX
Ding
Xiao-Yan
XY
Wang
Xin
X
Hu
Yi-Ping
YP
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
C069077:BMI1 protein, human; D015815:Cell Adhesion Molecules; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1