Breast Cancer Upregulating Genes in Stromal Cells by LINE-1 Hypermethylation and Micrometastatic Detection

Abstract

Changes in the methylation level of genes containing LINE-1 alter host gene regulation. Aim: This study demonstrates that paracrine signaling of breast cancer influences the epigenetic regulation of stromal cells. Methods: We proved in vitro and in vivo breast cancer promoted LINE-1 methylation exists exclusively in female stromal cells. Results: Genes containing LINE-1 of breast cancer stromal cells were upregulated. Furthermore, one of the genes, MUC-1, was demonstrated to have expression in plasma cells from the lymph nodes of patients with lymph node metastasis or micrometastasis. Conclusion: Breast cancer sends a paracrine signal to stroma cells causing LINE-1 epigenetic regulation. Moreover, the regulated genes in stroma cells are potential biomarkers for detecting breast cancer micrometastasis.

Keywords::

• breast cancer
• LINE-1 hypermethylation
• tumor supporting tissue

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2015-0007

Acknowledgements

The authors would like to thank V Boonyaratanakornkit and S Jirawatnotai for their breast cancer cell culture technical support and P Pavasant for his fibroblast cell culture technical support. They also thank T Chaichana for technical support in immunohistochemistry process.

Authors contributions

The experiments were conducted and designed by A Mutirangura, N Kitkumthorn and C Puttipanyalears. The experiments were performed by C Puttipanyalears, N Kitkumthorn and S Buranapraditkun. The clinical samples were recruited and collected by S Keelawat, N Kitkumthorn and C Puttipanyalears. The results were analyzed and interpreted by A Mutirangura, N Kitkumthorn, C Puttipanyalears and S Keelawat. C Puttipanyalears wrote the manuscript. A Mutirangura and N Kitkumthorn reviewed and edited the manuscript. All authors read and approved the final manuscript.

Financial & competing interests disclosure

This study was financially supported by a Research Chair Grant 2011 from the National Science and Technology Development Agency (NSTDA), Thailand grant number RSA5580013 from the Thailand Research Fund, The Royal Golden Jubilee PhD Program (grant number PHD/0053/2549) and the Anantara Siam Bangkok Hotel Care for Cancer 2016 Fun Run in coordination with the Thai Red Cross Society and Chulalongkorn University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was financially supported by a Research Chair Grant 2011 from the National Science and Technology Development Agency (NSTDA), Thailand grant number RSA5580013 from the Thailand Research Fund, The Royal Golden Jubilee PhD Program (grant number PHD/0053/2549) and the Anantara Siam Bangkok Hotel Care for Cancer 2016 Fun Run in coordination with the Thai Red Cross Society and Chulalongkorn University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.