Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer
Abstract
The Sprouty gene family negatively regulates growth factor-induced receptor tyrosine kinase signaling with a potential tumor suppressor function in cancer. I have demonstrated that Sprouty1 is down-regulated in human prostate cancer. The purpose of the present study is to elucidate the relative contribution of transcription regulation and epigenetic DNA methylation changes in regulating Sprouty1 expression in human prostate cancer. Using transient transfection analysis in prostate cancer cell lines; I have shown that gene knockdown of two transcription factor families: EGR (1 and 2), and GATA (2 and 4) induced Sprouty1 protein expression as determined by western blot analysis suggesting that these transcription factors may negatively regulate Sprouty1 expression. In addition, methylation modification of the Sprouty1 promoter by treatment with SssI methylase abolished promoter activity in transiently transfected prostate cancer cells, whereas global demethylation induced Sprouty1 expression. Observations reported here demonstrate transcriptional repression and/or epigenetic inactivation of Sprouty1 expression in prostate cancer cells. I have observed strong transcriptional activity in the prostate cancer cell lines even though Sprouty1 expression is down-regulated, suggesting that epigenetic modification of the binding sites for transcription factors such as Sp1 may result in a refractory transcriptional response even in the presence of necessary trans-acting activities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2007
- Accession Number
- ADA478427
Entities
People
- Bernard Kwabi-addo
Organizations
- Howard University