Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer.
Bottom Line: Comprehensive understanding of the regulation mechanism of Shh in cancer cells is necessary to find an effective approach to selectively block its tumorigenic function.Moreover, in vitro data demonstrated that both NF-κB activation and hypomethylation in promoter region were positively associated with the overexpression of Shh.Furthermore, the biological function data indicated that overexpressed Shh enhanced the self-renewal capacity and migration ability of breast cancer cells, which could be augmented by promoter demethylation and NF-κB activation.
Affiliation: Department of Pharmacology, College of Life Science and Biopharmaceutical of Shenyang Pharmaceutical University, Shenyang, China.Show MeSH
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Mentions: To elucidate the characteristics of Shh promoter region, a series of pGL3-Shh-promter-luciferase vectors were constructed, and the activities of reporter genes were measured after being transfected in MDA-MB-231 cells for 24 h. Our results indicated that pGL3-Shh-P1 reporter and pGL3-Shh-P2 reporter displayed similar activity, suggesting that the transcription factor Sp1 binding site has no significant effect on activity of the Shh promoter (Fig.3a). In contrast, the deletion of the NF-κB binding site (pGL3-Shh-P3 reporter) resulted in an obvious decrease (Fig.3a), indicating that the NF-κB binding site is crucial to maintain transcription activity of the Shh promoter.
Affiliation: Department of Pharmacology, College of Life Science and Biopharmaceutical of Shenyang Pharmaceutical University, Shenyang, China.