title: Phosphatase and tensin homolog on chromosome 10 is phosphorylated in primary effusion lymphoma and Kaposi's sarcoma.
abstract: Primary effusion lymphoma (PEL) is a non-Hodgkin's B-cell lymphoma driven by Kaposi's sarcoma-associated herpesvirus. It is uniquely sensitive to mTOR, PI3K, and Akt inhibitors; however, the basis of this requirement for the mTOR pathway remains to be elucidated. The phosphatase and tensin homolog gene (PTEN) on chromosome 10 controls the first step in the phosphatidylinositol 3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway and is genetically inactivated in many solid tumors. We find an absence of PTEN deletions, mutations, or protein mislocalization in PEL. However, we find consistent hyperphosphorylation at serine 380 of PTEN, which is an inactivating modification, in PEL cell lines and in tumor xenografts. We also evaluated a large tissue microarray of Kaposi's sarcoma biopsies and observed concordant high levels of phospho-PTEN, phospho-Akt, and phospho-S6 ribosomal protein. Reintroduction of PTEN into PEL inhibited colony formation in soft agar, verifying the functional dependence of PEL on PI3K signaling. This was also true for PEL cell lines that carried mutant p53 and for KS-like cell lines. Activating PTEN in these cancers may yield a new treatment strategy for PEL, KS, and similar PTEN wild-type lymphomas.
authors.affiliation: Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USA.
authors.forename: Debasmita
authors.initials: D
authors.lastname: Roy
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
mesh_terms: D000818:Animals; D001706:Biopsy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D054685:Lymphoma, Primary Effusion / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000201:enzymology* / Q000473:pathology*; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D038601:Ribosomal Protein S6; D010768:Phosphoserine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human