2006
DOI: 10.1158/1535-7163.mct-05-0147
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Differential cellular and molecular effects of bortezomib, a proteasome inhibitor, in human breast cancer cells

Abstract: The cellular and molecular effects of the proteasome inhibitor bortezomib on breast cancer cells are as yet poorly characterized.

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Cited by 102 publications
(111 citation statements)
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“…The activity demonstrated in the present study does not appear to arise from the mechanism proposed, by which bortezomib reduces AAG concentrations through inhibition of IL-6 and consequently increases docetaxel efficacy, as mean AAG concentrations increases from baseline at nearly all time points across bortezomib dose levels. Other cellular and molecular effects of bortezomib may be involved; recently published results demonstrating its differential effects in breast cancer cells may be relevant in designing mechanism-based combination treatments (Codony-Servat et al, 2006).…”
Section: Discussionmentioning
confidence: 99%
“…The activity demonstrated in the present study does not appear to arise from the mechanism proposed, by which bortezomib reduces AAG concentrations through inhibition of IL-6 and consequently increases docetaxel efficacy, as mean AAG concentrations increases from baseline at nearly all time points across bortezomib dose levels. Other cellular and molecular effects of bortezomib may be involved; recently published results demonstrating its differential effects in breast cancer cells may be relevant in designing mechanism-based combination treatments (Codony-Servat et al, 2006).…”
Section: Discussionmentioning
confidence: 99%
“…Although no direct links between proteasome inhibitors and inhibition of VEGF or PDGFRs have been reported, several studies have noted decreased VEGF expression following treatment with proteasome inhibitors (35,36). Proteasome inhibitors have also been shown to decrease phosphorylated Akt levels in a process thought to be related to accumulation of the inhibitor PTEN (37) or inhibition of upstream pathways (38). We did not see decreased Akt phosphorylation with bortezomib alone at synergistic concentrations, which may be due to either cell linespecific effects or dose differences.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, PS-341 exhibits a wide range of antitumor activity and increases the activity of multiple chemotherapeutic agents (5,6,22,23). Although PS-341 was found to be active against breast cancer cell lines, in vivo models and phase Ⅰ clinical trials have found it ineffective for breast cancer when used as a single agent (24), and limited efficacy of PS-341 has been noted in combination with several chemotherapeutic agents (25,26).…”
Section: Discussionmentioning
confidence: 99%
“…The proteasome inhibitor bortezomib (PS-341) has been licensed for the treatment of refractory multiple myeloma and mantle cell lymphoma. Although PS-341 is active against breast cancer cell lines (5,6), the effect of PS-341 on RANKLinduced breast cancer cell migration has yet to be clarified.…”
Section: Introductionmentioning
confidence: 99%