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S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer

Oncogene volume 29, pages 2083–2092 (2010)Cite this article

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Abstract

S100A7 promotes aggressive features in breast cancer, although regulation of its expression is poorly understood. As S100A7 associates with inflammation in skin and breast tissue, we hypothesized that inflammatory cytokines may regulate S100A7 in breast cancer. We therefore examined the effects of several cytokines, among which oncostatin-M (OSM) and the related cytokine, interleukin (IL)-6, showed the most significant effects on S100A7 expression in breast tumor cells in vitro. Both cytokines consistently induced S100A7 expression in three cell lines (MCF7, T47D and MDA-MB-468) in a dose- and time-dependent manner. Induction of S100A7 was inhibited by blockade of STAT3, phosphatidylinositol 3 kinase (PI3K) and ERK1/2 signaling and small interference RNA (siRNA)-mediated knockdown of S100A7 eliminated the promigratory effects of OSM treatment. S100A7 mRNA levels in a case-control cohort of breast tumors (n=20) were significantly associated with expression of the OSM receptor β (OSMRβ) chain (P=0.0098). This association was confirmed using publicly available microarray data from an independent breast tumor cohort (n=201, P=0.0005) and a correlation between S100A7 and poor patient survival was observed specifically in cases with high OSMRβ expression (HR=2.35; P=0.0396; n=85). We conclude that inflammatory cytokines can regulate S100A7 expression and that S100A7 may mediate some of their effects in breast cancer.

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Acknowledgements

We thank Rebecca Barnes for editorial and Melanie Olson for technical assistance, Dr Robert Burke for assistance with microscopy, and Dr Jiaxu Wang, Dr Julian Lum, Eric Tran and Darin Wick for helpful discussion. We also wish to thank the investigators responsible for making the UNC microarray data set publically available. PHW holds an operating grant from the Canadian Institutes of Health Research (CIHR, grant #MOP-64349). This study was supported by the Manitoba Breast Tumor Bank (supported by CIHR grant #PRG80155), a member of the Canadian Tumor Repository Network. NRW is supported by a US DOD Breast Cancer Research Program predoctoral traineeship award.

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  1. Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, British Columbia, Canada

    N R West & P H Watson

  2. Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada

    N R West & P H Watson

  3. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    P H Watson

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Correspondence to P H Watson.

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West, N., Watson, P. S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer. Oncogene 29, 2083–2092 (2010). https://doi.org/10.1038/onc.2009.488

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