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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hyun, T. Articles by Li, W. Search for Related Content PubMed PubMed Citation Articles by Hyun, T. Articles by Li, W. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2000, Vol. 96, No. 10, pp. 3560-3568 NEOPLASIA Loss of PTEN expression leading to high Akt activation in human multiple myelomas Teresa Hyun, Alan Yam, Salvatore Pece, Xiaozhen Xie, Jie Zhang, Toru Miki, J. Silvio Gutkind, and Weiqun Li From the Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD; Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC ; Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research; and Molecular Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, Bethesda, MD. Mouse plasma cell tumor (PCT) and human multiple myeloma (MM) are terminal B-cell malignancies sharing many similarities. Our recent work demonstrated that activation of the insulin-like growth factor receptor (IGF-IR)/insulin receptor substrate (IRS)/phosphatidylinositol 3' kinase (PI 3'K) pathway was evident in the tumor lines derived from both species. Although PI 3'K activity was higher in mouse tumor lines than that in human tumors, activation of Akt serine/threonine kinase was markedly lower in mouse lines. This discrepancy prompted us to test the status of PTEN tumor suppressor gene, as it has been shown to be a negative regulator of PI 3'K activity. Although all the mouse lines expressed intact PTEN, 2 of the 4 human lines (47 and OPM2) possessing the highest Akt activity lost PTEN expression. Sequencing analysis demonstrated that the PTEN gene contains a deletion spacing from exon 3 to exon 5 or 6 in the 47 line and from exon 3 to 7 in the OPM2 line. Restoration of PTEN expression suppressed IGF-I-induced Akt activity, suggesting that loss of PTEN is responsible for uncontrolled Akt activity in these 2 lines. Despite the expression of PTEN with the concomitant low Akt activity in all mouse PCT lines, their p70S6K activities were generally higher than those in 3 human MM lines, arguing for specific negative regulation of Akt, but not p70S6K by PTEN. These results suggest that p70S6K and Akt may be differentially used by the plasma cell tumors derived from mice and humans, respectively. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Salazar, T. Kashiwada, P. Krejci, P. Muchowski, D. Donoghue, W. R. Wilcox, and L. M. Thompson A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells Hum. Mol. Genet., June 1, 2009; 18(11): 1951 - 1961. [Abstract] [Full Text] [PDF] P. Frost, Y. Shi, B. Hoang, J. Gera, and A. Lichtenstein Regulation of D-cyclin translation inhibition in myeloma cells treated with mammalian target of rapamycin inhibitors: rationale for combined treatment with extracellular signal-regulated kinase inhibitors and rapamycin Mol. 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