Title : Inhibition of GSK-3β activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells.

Pub. Date : 2014

PMID : 24407515






8 Functional Relationships(s)
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1 MCF-7/GSK-3beta(KD) cells were more resistant to doxorubicin and tamoxifen compared with either MCF-7/GSK-3beta(WT) or MCF-7/GSK-3beta(A9) cells. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens
2 In the presence and absence of doxorubicin, the MCF-7/GSK-3beta(KD) cells formed more colonies in soft agar compared with MCF-7/GSK-3beta(WT) or MCF-7/GSK-3beta(A9) cells. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens
3 However, resistance to doxorubicin and tamoxifen were alleviated in MCF-7/GSK-3beta(KD) cells upon co-treatment with an MEK inhibitor, indicating regulation of this resistance by the Raf/MEK/ERK pathway. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens
4 Treatment of MCF-7 and MCF-7/GSK-3beta(WT) cells with doxorubicin eliminated the detection of S9-phosphorylated GSK-3beta, while total GSK-3beta was still detected. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens
5 Treatment of MCF-7 and MCF-7/GSK-3beta(WT) cells with doxorubicin eliminated the detection of S9-phosphorylated GSK-3beta, while total GSK-3beta was still detected. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens
6 Treatment of MCF-7 and MCF-7/GSK-3beta(WT) cells with doxorubicin eliminated the detection of S9-phosphorylated GSK-3beta, while total GSK-3beta was still detected. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens
7 In contrast, S9-phosphorylated GSK-3beta was still detected in MCF-7/GSK-3beta(KD) and MCF-7/GSK-3beta(A9) cells, indicating that one of the effects of doxorubicin on MCF-7 cells was suppression of S9-phosphorylated GSK-3beta, which could result in increased GSK-3beta activity. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens
8 Taken together, these results demonstrate that introduction of GSK-3beta(KD) into MCF-7 breast cancer cells promotes resistance to doxorubicin and tamoxifen, but sensitizes the cells to mTORC1 blockade by rapamycin. Doxorubicin glycogen synthase kinase 3 beta Homo sapiens