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Stat5 synergizes with T cell receptor/antigen stimulation in the development of lymphoblastic lymphoma 总被引:7,自引:0,他引:7 下载免费PDF全文
Kelly JA Spolski R Kovanen PE Suzuki T Bollenbacher J Pise-Masison CA Radonovich MF Lee S Jenkins NA Copeland NG Morse HC Leonard WJ 《The Journal of experimental medicine》2003,198(1):79-89
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Liang K Jin W Knuefermann C Schmidt M Mills GB Ang KK Milas L Fan Z 《Molecular cancer therapeutics》2003,2(4):353-360
The phosphatidylinositol 3-kinase (PI-3K)/Akt pathway, regulated by its upstream growth factor receptor tyrosine kinases, plays a critical role in promoting cell proliferation and inhibiting cell death. The aim of this study was to determine whether the PI-3K/Akt activity contributes to the resistance of human breast cancer cells to ionizing radiation and whether inhibition of the PI-3K/Akt pathway could sensitize human breast cancer cells to radiotherapy. To determine a causal relationship between the activity of Akt and radioresistance in human breast cancer cells, MCF7 cells, transfected with constitutively active H-Ras (RadG12V) or constitutively active Akt, were chosen for analysis of the cell clonogenic survival fraction and induction of apoptosis after ionizing radiation. The PI-3K-specific inhibitor LY294002 was used to examine whether inhibition of PI-3K could sensitize these cells to radiation treatment. Our results indicate that the expression of constitutively active Ras (which activated Akt in a PI-3K-dependent manner) and the expression of constitutively active Akt (which caused a PI-3K-independent activation of Akt) each increased cellular resistance to radiation. Inhibition of PI-3K with LY294002 reverted the constitutively active Ras-mediated radioresistance but not the constitutively active Akt-mediated radioresistance. Our data suggest that Akt may be a potential target for enhancing the response to radiotherapy in patients with breast cancer. 相似文献
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Marotta LL Almendro V Marusyk A Shipitsin M Schemme J Walker SR Bloushtain-Qimron N Kim JJ Choudhury SA Maruyama R Wu Z Gönen M Mulvey LA Bessarabova MO Huh SJ Silver SJ Kim SY Park SY Lee HE Anderson KS Richardson AL Nikolskaya T Nikolsky Y Liu XS Root DE Hahn WC Frank DA Polyak K 《The Journal of clinical investigation》2011,121(7):2723-2735
Intratumor heterogeneity is a major clinical problem because tumor cell subtypes display variable sensitivity to therapeutics and may play different roles in progression. We previously characterized 2 cell populations in human breast tumors with distinct properties: CD44+CD24- cells that have stem cell-like characteristics, and CD44-CD24+ cells that resemble more differentiated breast cancer cells. Here we identified 15 genes required for cell growth or proliferation in CD44+CD24- human breast cancer cells in a large-scale loss-of-function screen and found that inhibition of several of these (IL6, PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation. We found that the IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts. Our results highlight the differences between distinct breast cancer cell types and identify targets such as JAK2 and Stat3 that may lead to more specific and effective breast cancer therapies. 相似文献
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Taub R 《The Journal of clinical investigation》2003,112(7):978-980
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