Proteomic screening of 725 antibodies simultaneously using antibody microarray technology to identify proteins associated with radiotherapy resistance in breast cancer cells

Smith, Laura; Qutob, O; Watson, MB; Beavis, A W; Lind, MJ; Drew, PJ; Cawkwell, Lynn

doi:10.1186/bcr1945

Cited by 1 publication

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“…4A and B). Such a role for L‐plastin has also been identified in radiotherapy resistant clones derived from MCF‐7, T47D and MDA‐MB‐231 breast cancer cell lines [39], although the resistance mechanism to TNF‐α and radiotherapy are fundamentally different.…”

Section: Resultsmentioning

confidence: 99%

The actin filament cross‐linker L‐plastin confers resistance to TNF‐α in MCF‐7 breast cancer cells in a phosphorylation‐dependent manner

Janji¹,

Vallar²,

Tanoury

et al. 2010

J Cellular Molecular Medi

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We used a tumour necrosis factor (TNF)-α resistant breast adenocarcinoma MCF-7 cell line to investigate the involvement of the actin cytoskeleton in the mechanism of cell resistance to this cytokine. We found that TNF resistance correlates with the loss of cell epithelial properties and the gain of a mesenchymal phenotype, reminiscent of an epithelial-to-mesenchymal transition (EMT). Morphological changes were associated with a profound reorganization of the actin cytoskeleton and with a change in the repertoire of expressed actin cytoskeleton genes and EMT markers, as revealed by DNA microarray-based expression profiling. L-plastin, an F-actin cross-linking and stabilizing protein, was identified as one of the most significantly up-regulated genes in TNF-resistant cells. Knockdown of L-plastin in these cells revealed its crucial role in conferring TNF resistance. Importantly, overexpression of wild-type L-plastin in TNF-sensitive MCF-7 cells was sufficient to protect them against TNF-mediated cell death. Furthermore, we found that this effect is dependent on serine-5 phosphorylation of L-plastin and that non-conventional protein kinase C isoforms and the ceramide pathway may regulate its phosphorylation state. The protective role of L-plastin was not restricted to TNF-α resistant MCF-7 cells because a correlation between the expression of L-plastin and the resistance to TNF-α was observed in other breast cancer cell lines. Together, our study discloses a novel unexpected role of the actin bundling protein L-plastin as a cell protective protein against TNF-cytotoxicity.

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Section: Resultsmentioning

confidence: 99%