Oncoprotein BMI‐1 induces the malignant transformation of HaCaT cells
Oncoprotein BMI‐1 induces the malignant transformation of HaCaT cells
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DOI：
10.1002/jcb.21969
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发表时间：
2009
影响因子：
4
通讯作者：
Qian Wang;Wen-lin Li;Pu You;Juan Su;Ming-hua Zhu;D. Xie;Haiying Zhu;Zhiying He;Jianxiu Li;Xiaoyan Ding;Xin Wang;Yi-Ping Hu
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文献类型：
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作者：
Qian Wang;Wen-lin Li;Pu You;Juan Su;Ming-hua Zhu;D. Xie;Haiying Zhu;Zhiying He;Jianxiu Li;Xiaoyan Ding;Xin Wang;Yi-Ping Hu
BMI - 1 （B细胞特异性Moloney小鼠白血病病毒整合位点1）是一种新的致癌基因，近年来因其参与多种肿瘤的发生而受到广泛关注。最近的证据表明，BMI‐1在肿瘤性皮肤病变中高度表达。然而，BMI‐1表达失调是否是皮肤细胞转化的原因尚不清楚。在这项研究中，我们在人角质形成细胞系HaCaT中稳定表达BMI‐1。野生型BMI - 1的表达诱导HaCaT细胞在体外发生恶性转化。更重要的是，我们发现BMI‐1的表达促进了体内鳞状细胞癌的形成。此外，我们发现BMI‐1的表达导致肿瘤抑制因子p16INK4a和p14ARF、细胞粘附分子E‐Cadherin和分化相关因子KRT6的下调。因此，我们的研究结果表明，BMI‐1失调确实可能通过促进细胞周期进展和增加细胞流动性，导致角化细胞转化和肿瘤发生。j .细胞。生物化学学报，26(6):516 - 524,2009。©2008 Wiley‐Liss, Inc。
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.