PI3K/AKT/mTOR通路
生物
细胞生长
癌症研究
免疫组织化学
RPTOR公司
病理
信号转导
医学
细胞生物学
免疫学
生物化学
作者
Raina Patel,Imran Ahmad,Christine E. Sheehan,Jeffrey S. Ross,George D. Wilner,Alida Hayner‐Buchan,Tipu Nazeer
出处
期刊:Blood
[American Society of Hematology]
日期:2007-11-16
卷期号:110 (11): 1573-1573
标识
DOI:10.1182/blood.v110.11.1573.1573
摘要
Abstract Background: The mammalian target of rapamycin (mTOR), plays a major role in regulating cell growth. The activated form of mTOR (phosphorylated mTOR) mediates its effects through mitogen and nutrient dependant signal transduction that regulates mRNA translation. Levels of phosphorylated mTOR (p-mTOR) have been shown to correlate with cell proliferation and inhibition of the mTOR pathway has shown therapeutic promise in some tumors. Information on the role of p-mTOR in hematopoietic malignancies is limited. The aim of the current study is to evaluate the expression of p-mTOR in diffuse large B-cell lymphomas. Design: Formalin-fixed paraffin-embedded tissue sections from 45 DLBCLs were immunostained by an automated method (Ventana Medical Systems, Inc., Tucson, AZ) using p-mTOR rabbit monoclonal antibody (IHC specific Ser2448/49F9; Cell Signaling Technology, Inc., Danvers, MA). Immunoreactivity (cytoplasmic with membranous accentuation) was semiquantitatively assessed based on p-mTOR stain intensity (none, weak, moderate, intense) and distribution (none, focal<10%, regional 11–50%, diffuse>50%). Staining was correlated with histologic and prognostic factors. Results: Membranous/cytoplasmic p-mTOR immunoreactivity was present in 88% of DLBCLs and correlated with advanced tumor stage, with 100% advanced stage versus 73% low stage tumors expressing membranous/cytoplasmic p-mTOR protein (p=0.002). One hundred percent of cases with complete absence of p-mTOR immunoreactivity were low stage DLBCLs. Conclusion: Membranous/cytoplasmic protein expression of p-mTOR correlates with advanced stage in DLBCL. Activated mTOR may play an important role in disease progression and provide a target for therapy in DLBCL. Further studies of the m-TOR pathway in hematopoietic malignancies appear warranted.
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