Abstract：
:Chemokines play the key role in initiating immune responses by regulating the attraction and homing of immune cells to the lymphoid and nonlymphoid tissues. CXCL14 is a chemokine that in tumors may act as chemoattractant for monocytes and dendritic cells (DC), which may modulate antitumor immune responses in certain cancers. In this study, we investigated the mechanisms of loss of CXCL14 in prostate cancer cells. Cell treatment with the demethylating agent 5-aza-2-deoxycytidine resulted in the recovery of CXCL14 mRNA and protein expression. Hypermethylated CpG island sequences encompassing the CXCL14 gene promoter were identified. The restoration of CXCL14 by 5-aza-2-deoxycytidine treatment had functional impact, based on the DC chemoattractant activity of conditioned medium from drug-treated cells. Conversely, CXCL14 removal from conditioned media by affinity chromatography abolished its chemotactic properties, confirming that functionally active CXCL14 was generated in prostate cancer cells by relieving its transcriptional silencing with 5-aza-2-deoxycytidine. Our findings offer the first direct evidence for epigenetic regulation of chemokine expression in tumor cells.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Song EY,Shurin MR,Tourkova IL,Gutkin DW,Shurin GVdoi
10.1158/0008-5472.CAN-10-0427subject
Has Abstractpub_date
2010-06-01 00:00:00pages
4394-401issue
11eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-0427journal_volume
70pub_type
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