國家衛生研究院 NHRI:Item 3990099045/3031
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3031


    Title: Profiling the downstream genes of tumor suppressor PTEN in lung cancer cells by complementary DNA microarray
    Authors: Hong, TM;Yang, PC;Peck, K;Chen, JJW;Yang, SC;Chen, YC;Wu, CW
    Contributors: National Institute of Cancer Research
    Abstract: The phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor suppressor gene with sequence homology to tyrosine phosphatases and the cytoskeletal proteins tensin and auxilin. PTEN has recently been shown to inhibit cell migration and the spreading and formation of focal adhesions. This study investigated the role of PTEN in carcinoma invasion in a lung-cancer cell line and examined the downstream genes regulated by PTEN. We have previously established a cell-line model in human lung adenocarcinoma with different invasive abilities and metastatic potentials. Examining PTEN gene expression in these cell lines, we found that a homozygous deletion in exon 5 is associated with high invasive ability. We then constructed stable constitutive and inducible wild-type PTEN-overexpressed transfectants in the highly invasive cell line CL1-5. We found that an overexpression of PTEN can inhibit invasion in lung cancer cells. To further explore the downstream genes regulated by PTEN, a high-density complementary DNA (cDNA) microarray technique was used to profile gene changes after PTEN overexpression. Our results indicate a panel of genes that can be modulated by PTEN. PTEN overexpression downregulated genes, including integrin alpha(6), laminin beta(3), heparin-binding epidermal growth factor-like growth factor, urokinase-type plasminogen activator, myb protein B, Akt2, and some expressed sequence tag (EST) clones. In contrast, PTEN overexpression upregulated protein phosphatase 2A1B, ubiquitin protease (unph), secreted phosphoprotein 1, leukocyte elastase inhibitor, nuclear factor-kappa B, cyclic adenosine monophosphate response element binding protein, DNA ligase 1, heat shock protein 90, and some EST genes. Northern hybridization and flow cytometry analysis also confirmed that PTEN overexpression results in the reduced expression of the integrin alpha(6) subunit. The results of this study indicate that PTEN overexpression may inhibit lung cancer invasion by downregulation of a panel of genes including integrin alpha(6) The cDNA microarray technique may be an effective tool to study the downstream function of a tumor suppressor gene.
    Keywords: Biochemistry & Molecular Biology;Cell Biology;Respiratory System
    Date: 2000-09
    Relation: American Journal of Respiratory Cell and Molecular Biology. 2000 Sep;23(3):355-363.
    Link to: http://ajrcmb.atsjournals.org/cgi/content/abstract/23/3/355
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1044-1549&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000089561100015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0033827724
    Appears in Collections:[Cheng-Wen Wu(1996-2008)] Periodical Articles

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