α4 is highly expressed in carcinogen-transformed human cells and primary human cancers

被引：39

作者：

Chen, L-P ^{[1
]}

Lai, Y-D ^{[1
,2
]}

Li, D-C ^{[1
]}

Zhu, X-N ^{[1
]}

Yang, P. ^{[1
]}

Li, W-X ^{[1
,3
]}

Zhu, W. ^{[3
]}

Zhao, J. ^{[4
]}

Li, X-D ^{[5
]}

Xiao, Y-M ^{[1
]}

Zhang, Y. ^{[6
]}

Xing, X-M ^{[1
]}

Wang, Q. ^{[1
]}

Zhang, B. ^{[1
]}

Lin, Y-C ^{[1
]}

Zeng, J-L ^{[1
]}

Zhang, S-X ^{[1
]}

Liu, C-X ^{[1
]}

Li, Z-F ^{[1
]}

Zeng, X-W ^{[1
]}

Lin, Z-N ^{[1
]}

Zhuang, Z-X ^{[1
,7
]}

Chen, W. ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Publ Hlth, Guangdong Prov Key Lab Food Nutr & Hlth, Dept Toxicol,Fac Prevent Med, Guangzhou 510080, Guangdong, Peoples R China

[2] Guangzhou Med Coll, Inst Chem Carcinogenesis, Guangzhou, Guangdong, Peoples R China

[3] Guangzhou Ctr Dis Control, Unit Toxicol, Guangzhou, Guangdong, Peoples R China

[4] Guangzhou Med Univ, Affiliated Canc Hosp, Dept Thorac Surg, Guangzhou, Guangdong, Peoples R China

[5] Sun Yat Sen Univ, Ctr Canc, Dept Thorac Surg, Guangzhou 510275, Guangdong, Peoples R China

[6] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China

[7] Shenzhen Ctr Dis Control & Prevent, Dept Toxicol, Shenzhen, Peoples R China

来源：

ONCOGENE | 2011年 / 30卷 / 26期

关键词：

alpha; 4; protein phosphatase 2A; cell transformation; human cancers; PROTEIN PHOSPHATASE 2A; SENSITIVE SIGNAL-TRANSDUCTION; TUMOR-SUPPRESSOR PP2A; CATALYTIC SUBUNIT; UBIQUITIN LIGASE; BINDING PROTEIN; OPITZ-SYNDROME; A-ALPHA; TARGETS; GROWTH;

D O I：

10.1038/onc.2011.20

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A regulator of the protein phosphatase 2A (PP2A), alpha 4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of alpha 4 in human cell transformation and tumorigenesis, we show that alpha 4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a) pyrene, aflatoxin B(1), N-methyl-N'-nitro- N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of a4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that a4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated alpha 4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of alpha 4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed alpha 4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of alpha 4 through specific binding to the 3'-untranslated region of alpha 4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that alpha 4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced alpha 4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis. Oncogene (2011) 30, 2943-2953; doi:10.1038/onc.2011.20; published online 21 February 2011

引用

页码：2943 / 2953

页数：11

共 44 条

[1]

Involvement of PP2A in viral and cellular transformation [J].