کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5939317 1573425 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phosphatase and Tensin Homolog on Chromosome 10 Is Phosphorylated in Primary Effusion Lymphoma and Kaposi's Sarcoma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Phosphatase and Tensin Homolog on Chromosome 10 Is Phosphorylated in Primary Effusion Lymphoma and Kaposi's Sarcoma
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The American Journal of Pathology - Volume 179, Issue 4, October 2011, Pages 2108-2119
نویسندگان
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