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[alpha]4 is highly expressed in carcinogen-transformed human cells and primary human cancers.(ORIGINAL ARTICLE)(Report)

Chen, L. - P. ; Lai, Y. - D. ; Li, D. - C. ; Zhu, X. - N. ; Yang, P. ; Li, W. - X. ; Zhu, W. ; Zhao, J. ; Li, X - D ; Xiao, Y. - M. ; Zhang, Y. ; Xing, X. - M. ; Wang, Q. ; Zhang, B. ; Lin, Y. - C. ; Zeng, J. - L. ; Zhang, S. - X. ; Liu, C. - X. ; Li, Z. - F. ; Zeng, X. - W. ; Lin, Z. - N. ; Zhuang, Z. - X. ; Chen, W.

Oncogene, June 30, 2011, Vol.30(26), p.2943(11) [Periódico revisado por pares]

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  • Título:
    [alpha]4 is highly expressed in carcinogen-transformed human cells and primary human cancers.(ORIGINAL ARTICLE)(Report)
  • Autor: Chen, L. - P. ; Lai, Y. - D. ; Li, D. - C. ; Zhu, X. - N. ; Yang, P. ; Li, W. - X. ; Zhu, W. ; Zhao, J. ; Li, X - D ; Xiao, Y. - M. ; Zhang, Y. ; Xing, X. - M. ; Wang, Q. ; Zhang, B. ; Lin, Y. - C. ; Zeng, J. - L. ; Zhang, S. - X. ; Liu, C. - X. ; Li, Z. - F. ; Zeng, X. - W. ; Lin, Z. - N. ; Zhuang, Z. - X. ; Chen, W.
  • Assuntos: Cancer -- Genetic Aspects ; Cancer -- Care And Treatment ; Cancer -- Research ; Gene Expression -- Research ; Phosphatases -- Physiological Aspects ; Phosphatases -- Research
  • É parte de: Oncogene, June 30, 2011, Vol.30(26), p.2943(11)
  • Descrição: 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 a4ishighly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin [B.sup.1], N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, over-expression of [alpha]4 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 [alpha]4 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-intransformedcellsor 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 Keywords: [alpha]4; protein phosphatase 2A; cell transformation; human cancers
  • Idioma: English

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