PMC:3832756 / 25935-27171 JSONTXT

{"project":"2_test","denotations":[{"id":"23389114-9445477-29182905","span":{"begin":520,"end":522},"obj":"9445477"},{"id":"23389114-15380067-29182906","span":{"begin":616,"end":618},"obj":"15380067"},{"id":"23389114-11566616-29182907","span":{"begin":1084,"end":1086},"obj":"11566616"}],"text":"The argument for parallel, rather than linear inhibition of Akt and mTOR by SFN, is different dephosphorylation pattern of Akt and S6K1 kinases upon SFN treatment shown on immunoblotting (Fig. 4). Moreover, Akt activation is initiated by translocation to the plasma membrane mediated by docking of the PH domain in the N-terminal region of AKT to PI(3,4,5) P3 on the membrane, which results in a conformational change in Akt, exposing two critical amino acid residues (serine 473 and threonine 308) for phosphorylation [49]. On the other hand, generation of PI(3,4,5) P3 by PI3K is inhibited by mTOR-S6K1 signaling [48]. Thus, drop in p-S6K1 should rather stimulate Akt activation if SFN targets only one signal transducer. Interestingly, previous studies on sensitivity of the panel of breast cancer cell lines to mTOR inhibitor, CCI-779, revealed that cells sensitive to CCI-779 were estrogen receptor positive, overexpressed ErbB2 and/or had lost the tumor suppressor gene product PTEN. On the other hand, resistant cell lines (such as MDA MB 231) shared none of these properties [50]. In our model, SFN inhibits viability of all tested cell lines, including MDA MB 231, which also might indicate that it acts in at least two levels."}

{"project":"MyTest","denotations":[{"id":"23389114-9445477-29182905","span":{"begin":520,"end":522},"obj":"9445477"},{"id":"23389114-15380067-29182906","span":{"begin":616,"end":618},"obj":"15380067"},{"id":"23389114-11566616-29182907","span":{"begin":1084,"end":1086},"obj":"11566616"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"The argument for parallel, rather than linear inhibition of Akt and mTOR by SFN, is different dephosphorylation pattern of Akt and S6K1 kinases upon SFN treatment shown on immunoblotting (Fig. 4). Moreover, Akt activation is initiated by translocation to the plasma membrane mediated by docking of the PH domain in the N-terminal region of AKT to PI(3,4,5) P3 on the membrane, which results in a conformational change in Akt, exposing two critical amino acid residues (serine 473 and threonine 308) for phosphorylation [49]. On the other hand, generation of PI(3,4,5) P3 by PI3K is inhibited by mTOR-S6K1 signaling [48]. Thus, drop in p-S6K1 should rather stimulate Akt activation if SFN targets only one signal transducer. Interestingly, previous studies on sensitivity of the panel of breast cancer cell lines to mTOR inhibitor, CCI-779, revealed that cells sensitive to CCI-779 were estrogen receptor positive, overexpressed ErbB2 and/or had lost the tumor suppressor gene product PTEN. On the other hand, resistant cell lines (such as MDA MB 231) shared none of these properties [50]. In our model, SFN inhibits viability of all tested cell lines, including MDA MB 231, which also might indicate that it acts in at least two levels."}