Adenoviral transgene expression of MMAC/PTEN in human glioma cells inhibits Akt activation and induces anoikis

Michael A. Davies, Yiling Lu, Tetsuro Sano, Xianjun Fang, Ping Tang, Ruth LaPushin, Dimpy Koul, Robert Bookstein, David Stokoe, W. K.Alfred Yung, Gordon B. Mills, Peter A. Steck

    Research output: Contribution to journalArticle

    213 Scopus citations

    Abstract

    The MMAC/PTEN tumor suppressor gene encodes for a phosphatase that recently has been shown to have phosphotidylinositol phosphatase activity, implicating its possible involvement in phosphatidylinositol 3'-kinase- mediated signaling. To investigate possible alterations in growth factor- mediated signal transduction, an adenovirus containing MMAC/PTEN, Ad-MMAC, previously shown to inhibit growth and tumorigenicity in glioma cells, was used to acutely express the transgene. Human glioma cells infected with Ad- MMAC but not with control adenoviruses exhibited an inhibition of phosphorylation of both activating residues of Akt, Ser-473, and Thr-308, along with Akt's serine/threonine kinase activity, without significantly altering Akt expression. The effects of functional MMAC/PTEN expression were relatively specific, because members of several other growth factor-mediated signaling pathways showed no altered responses. The presence of MMAC/PTEN also inhibited phosphorylation of BAD, although no evidence of apoptosis in the in situ treated cells was observed. However, U251 glioma cells infected with Ad-MMAC were induced to undergo anoikis at a significantly higher rate than U251 cells treated with control viruses or mock infected with media. These results demonstrate that the acute administration of MMAC/PTEN results in the inhibition of Akt-mediated signaling, growth inhibition, and anoikis, implying that loss of MMAC/PTEN increases cellular proliferation and significantly augments a cell's survival potential during cellular processes that are associated with malignancy.

    Original languageEnglish (US)
    Pages (from-to)5285-5290
    Number of pages6
    JournalCancer Research
    Volume58
    Issue number23
    StatePublished - Dec 1 1998

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Davies, M. A., Lu, Y., Sano, T., Fang, X., Tang, P., LaPushin, R., Koul, D., Bookstein, R., Stokoe, D., Yung, W. K. A., Mills, G. B., & Steck, P. A. (1998). Adenoviral transgene expression of MMAC/PTEN in human glioma cells inhibits Akt activation and induces anoikis. Cancer Research, 58(23), 5285-5290.