BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer.
BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer.
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BMI1和Mel-18反向调节胃癌的发生和进展
DOI：
10.1186/1476-4598-9-40
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发表时间：
2010-02-21
期刊：
影响因子：
37.3
通讯作者：
Guo WJ
中科院分区：
文献类型：
--
作者：
Zhang XW;Sheng YP;Li Q;Qin W;Lu YW;Cheng YF;Liu BY;Zhang FC;Li J;Dimri GP;Guo WJ
背景BMI 1癌基因在包括胃癌在内的多种人类恶性肿瘤中过表达。除BMI 1外，哺乳动物细胞还表达与BMI 1密切相关的Mel-18。我们已经报道了Mel-18通过抑制乳腺癌细胞中BMI 1的表达和随后下调活化的AKT而作为潜在的肿瘤抑制剂发挥作用。然而，BMI 1过表达的机制以及Mel-18在其他癌症中的作用仍不清楚。本研究旨在探讨BMI 1和Mel-18在胃癌中的作用。BMI 1的过表达与临床分期、淋巴结转移有关，而Mel-18的表达与BMI 1呈负相关。BMI 1而不是Mel-18被认为是独立的预后因素。在胃癌细胞系中，通过Mel-18过表达或敲低BMI 1表达而下调BMI 1导致p16阳性细胞系中p16（p16 INK 4a或CDKN 2A）的上调以及p16阳性和p16阴性细胞系中磷酸化AKT的减少。BMI 1的下调也伴随着减少转化表型和迁移在p16阳性和p16阴性的胃癌细胞line.ConclusionsIn胃癌的背景下，BMI 1作为癌基因和梅尔18功能作为肿瘤抑制剂通过下调BMI 1。Mel-18和BMI 1可能通过p16和AKT依赖的生长调节途径调节肿瘤发生、细胞迁移和癌症转移。
BackgroundTheBMI1oncogene is overexpressed in several human malignancies including gastric cancer. In addition to BMI1, mammalian cells also express Mel-18, which is closely related to BMI1. We have reported that Mel-18 functions as a potential tumor suppressor by repressing the expression of BMI1 and consequent downregulation of activated AKT in breast cancer cells. However, the mechanisms of BMI1 overexpression and the role of Mel-18 in other cancers are still not clear. The purpose of this study is to investigate the role of BMI1 and Mel-18 in gastric cancer.ResultsBMI1 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of BMI1 correlated with advanced clinical stage and lymph node metastasis; while the expression of Mel-18 negatively correlated with BMI1. BMI1 but not Mel-18 was found to be an independent prognostic factor. Downregulation of BMI1 by Mel-18 overexpression or knockdown of BMI1 expression in gastric cancer cell lines led to upregulation of p16 (p16INK4a or CDKN2A) in p16 positive cell lines and reduction of phospho-AKT in both p16-positive and p16-negative cell lines. Downregulation of BMI1 was also accompanied by decreased transformed phenotype and migration in both p16- positive and p16-negative gastric cancer cell lines.ConclusionsIn the context of gastric cancer,BMI1acts as an oncogene and Mel-18 functions as a tumor suppressor via downregulation of BMI1. Mel-18 and BMI1 may regulate tumorigenesis, cell migration and cancer metastasis via both p16- and AKT-dependent growth regulatory pathways.
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DOI：
10.1073/pnas.0810715105
发表时间：
2008-12-23
影响因子：
11.1
作者：
Rychahou, Piotr G.;Kang, JungHee;Evers, B. Mark
通讯作者：
Evers, B. Mark
影响因子：
11.2
作者：
Datta, Sonal;Hoenerhoff, Mark J.;Dimri, Goberdhan P.
通讯作者：
Dimri, Goberdhan P.
影响因子：
5.3
作者：
Dimri, GP;Itahana, K;Campisi, J
通讯作者：
Campisi, J
影响因子：
11.2
作者：
Godlewski, Jakub;Nowicki, Michal O.;Lawler, Sean
通讯作者：
Lawler, Sean
影响因子：
12.8
作者：
Kim, Eun Kyoung;Yun, Sung Ji;Bae, Sun Sik
通讯作者：
Bae, Sun Sik