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Differential hypermethylation of SOCS genes in ovarian and breast carcinomas

Oncogene volume 23, pages 7726–7733 (2004)Cite this article

Abstract

Suppressor of cytokine signaling (SOCS) proteins have emerged as critical attenuators of cytokine-mediated processes, suggesting a role in the suppression of tumorigenesis. In the ovary and mammary gland, cytokines such as prolactin and IL-6 are important regulators of growth and differentiation. We have investigated whether silencing or inactivation of SOCS genes occurs in ovarian and breast carcinomas. The SOCS1 and SOCS2 CpG islands were found to be hypermethylated in 23 and 14% of primary ovarian cancers, respectively, whereas only SOCS1 was methylated in breast cancers (9%). Methylation of these genes did not occur in normal tissues. No correlation was apparent between methylation and loss of heterozygosity, and no somatic mutations were found in a large panel of carcinomas. Aberrant methylation of these SOCS genes correlated with transcriptional silencing in ovarian and breast cancer cell lines, since expression was induced by the demethylating agent 5-azadeoxycytidine. SOCS3 was not hypermethylated in either cancer type. Consistent with this data, SOCS1 and SOCS2 but not SOCS3 suppressed the growth of ovarian and breast cancer cells. Hypermethylation and silencing of specific SOCS genes in the ovary, and to a lesser extent in breast, may augment cytokine responsiveness in these tissues, thereby contributing to oncogenesis.

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Acknowledgements

We thank A Partanen for expert assistance with cryosectioning. We are grateful to N Jonas for help with cell culture, J Zhang for SOCS3 antibody, R Daly for providing MCF-7 EcoR cells, N Hayward for providing tumor samples, and I Haviv for ovarian cell cDNA. This work was supported by the Victorian Breast Cancer Research Consortium and the Bone Marrow Research Laboratories.

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research and Bone Marrow Research Laboratories, Royal Melbourne Hospital, Parkville, 3050, VIC, Australia

    Kate D Sutherland, Geoffrey J Lindeman, Sergio Wittlin & Jane E Visvader

  2. The Peter MacCallum Cancer Centre, East Melbourne, 8006, VIC, Australia

    David Y H Choong, Luci Brentzell, Wayne Phillips & Ian G Campbell

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  1. Kate D Sutherland
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  2. Geoffrey J Lindeman
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Correspondence to Jane E Visvader.

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Sutherland, K., Lindeman, G., Choong, D. et al. Differential hypermethylation of SOCS genes in ovarian and breast carcinomas. Oncogene 23, 7726–7733 (2004). https://doi.org/10.1038/sj.onc.1207787

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