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Wang Q, Li WL, You P et al.Oncoprotein BMI-1 induces the malignant transformation of HaCaT cells. J Cell Biochem 106:16-24

Department of Cell Biology, Second Military Medical University, Shanghai 200433, PR China.
Journal of Cellular Biochemistry (Impact Factor: 3.37). 01/2009; 106(1):16-24. DOI: 10.1002/jcb.21969
Source: PubMed

ABSTRACT 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.

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    • "Third, Bmi-1 and other PcG proteins are expressed at higher levels in tumors, both SCC (Reinisch et al., 2007; Balasubramanian et al., 2010), basal cell carcinoma (Reinisch et al., 2007) and melanoma (Bachmann et al., 2006; Mihic-Probst et al., 2007), although the Bmi-1 finding is somewhat controversial for melanoma, as one report describes reduced expression with clinical progression in malignant melanoma (Bachmann et al., 2008). Moreover, forced Bmi-1 expression in HaCaT cells causes transformation (Wang et al., 2009). This suggests that overexpression of these proteins may be one mechanism whereby tumor cells escape death through a mechanism that involves modulation of cell cycle and apoptotic processes (Lee et al., 2008; Balasubramanian et al., 2010). "
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