Reactivation of Syk gene by AZA suppresses metastasis but not proliferation of breast cancer cells
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Spleen tyrosine kinase (Syk) is reported to be involved in the suppression of proliferation and invasion of breast cancer. Methylation-mediated Syk gene silencing is found in a subset of breast cancer. In this study, we used a DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine (AZA), to restore Syk expression of breast cancer cells. Surprisingly, we found that AZA treatment could reestablish the expression of Syk, but not affect the proliferation of breast cancer cells. Moreover, tumor formation in situ by MDA-MB-435s treated with (+) or without (−) AZA in a nude mice MFP (Mammary fat pad) model did not show significant difference, too. Interestingly, pulmonary metastasis was still significantly suppressed in MDA-MB-435s(+) group (1/9 vs. 7/9). Our findings suggested Syk may be more correlated to metastasis rather than proliferation. This study implied a potential use of Syk methylation as a valuable biomarker to detect high metastatic potential cancerous lesions and the prospect of AZA to join the arsenal of drug candidates to be developed as a new reagent for management of advanced breast cancer.
KeywordsSpleen tyrosine kinase Breast cancer Metastasis AZA Reactivation
This research was supported in part by the National Natural Science Foundation of China (81071753), the Six Kinds of Outstanding Talent Foundation of Jiangsu Province (06-B-069), the Science and Education for Health foundation of Jiangsu Province (RC2007054), and the Natural Science Foundation of Jiangsu Province (BK2008476, BK2009438 and BK2010581). We thank Ji-Fu Wei (Clinical Experiment Center, the First Affiliated Hospital of Nanjing Medical University) for critical discussion in our study.
- 17.Mahabeleshwar GH, Kundu GC. Syk, a protein-tyrosine kinase, suppresses the cell motility and nuclear factor kappa B-mediated secretion of urokinase type plasminogen activator by inhibiting the phosphatidylinositol 3’-kinase activity in breast cancer cells. J Biol Chem. 2003;278(8):6209–21.PubMedCrossRefGoogle Scholar
- 35.Dong G, et al. Molecular profiling of transformed and metastatic murine squamous carcinoma cells by differential display and cDNA microarray reveals altered expression of multiple genes related to growth, apoptosis, angiogenesis, and the NF-kappaB signal pathway. Cancer Res. 2001;61(12):4797–808.PubMedGoogle Scholar