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- W3162712325 abstract "729 Tissue factor (TF) is a transmembrane protein that acts as a receptor for coagulation factor VII initiating the coagulation cascade, but also mediates intracellular signaling that is relevant to tumor growth, apoptosis and metastasis. High levels of TF expression have been observed in patients with advanced and metastatic cancer. Here we report that the expression of TF was regulated by the tumor suppressor PTEN and was associated with sensitivity to chemotherapeutic drugs in neuroblastoma. Two neuroblastoma cell lines SK-N-SH and SK-N-MC were examined for the expression of TF and PTEN as well as their response to doxorubicin-induced apoptosis. SK-N-SH expressing high levels of PTEN was TF negative and sensitive to doxorubicin, whereas SK-N-MC lacking PTEN expression expressed high levels of TF and was relatively resistant to doxorubicin. Inhibition of PTEN expression in SK-N-SH cells by PTEN siRNA upregulated TF expression. In contrast, TF was downregulated in SK-N-MC cells by enforced expression of PTEN as well as treatment with the PI3k/Akt inhibitor LY294002. Both PTEN gene transfection and LY294002 sensitized SK-N-MC cells to doxorubicin, which was also obtained by direct inhibition of TF with siRNA. These results suggest that the expression of TF is regulated by the PI3k/Akt pathway, and TF-mediated cellular signaling is at least one of the mechanisms by which loss of PTEN expression confers resistance to chemotherapy and cancer progression." @default.
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- W3162712325 date "2006-04-15" @default.
- W3162712325 modified "2023-10-14" @default.
- W3162712325 title "Loss of PTEN expression induces tissue factor expression and resistance to doxorubicin in neuroblastoma" @default.
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