Oncoprotein BMI-1 induces the malignant transformation of HaCaT cells

• Published in: Journal of cellular biochemistry Vol. 106; no. 1; pp. 16 - 24
• Main Authors: Wang, Qian, Li, Wen-Lin, You, Pu, Su, Juan, Zhu, Ming-Hua, Xie, Dong-Fu, Zhu, Hai-Yin, He, Zhi-Ying, Li, Jian-Xiu, Ding, Xiao-Yan, Wang, Xin, Hu, Yi-Ping
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2009
• Subjects: Animals; BMI-1; Cell Adhesion Molecules - metabolism; Cell Cycle; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cells, Cultured; HaCaT cell line; Humans; Keratinocytes - cytology; Keratinocytes - metabolism; Keratinocytes - pathology; malignant transformation; Mice; Mice, SCID; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Polycomb Repressive Complex 1; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; skin cancer; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.21969

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 tumore 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. J. Cell. Biochem. 106: 16–24, 2009. © 2008 Wiley‐Liss, Inc.