Matrix Metalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor (VEGF) Are Regulated by Histone Lysine Specific Demethylase 2 (LSD2) in Cultured Human Melanoma Cells
C Lian, B Lian, M-Y Hsu, Y Shi, B Woda, A Deng, R Han. University of Massachusetts, Worcester, MA; Brigham & Women's Hospital, Harvard Medical School, Boston; Brigham & Women's Hospital, Harvard Medical School, Boston, MA
Background: Matrix metalloproteinases (MMPs) and vascular endothelial growth factors (VEGFs) are involved in tumor invasion, metastasis and angiogenesis, and have been implicated as progression markers in melanoma. The molecular mechanisms that regulate the gene transcription of MMPs and VEGFs in melanoma are unknown. Histone modification is a key mechanism in epigenetic regulation of gene transcription, which is recently recognized as a crucial player in various physiological and pathological processes.
Design: Here we investigated the role the newly discovered lysine specific demethylase 2 (LSD2), a key enzyme in epigenetic regulation, in regulating both MMPs and VEGFs in melanoma by using cultured human melanoma cell line WM793. Knockdown of LSD2 expression was achieved by an adeno-associated virus (AAV) based siRNA delivery system. Both MMP-9 and VEGF mRNA expression was measured by quantitative real-time RT-PCR.
Results: LSD2 AAV siRNA effectively knocked down LSD2 gene transcription in cultured human melanoma cell line WM793. Both MMP-9 and VEGF mRNA expression was significantly down-regulated following LSD knockdown.
Conclusions: These findings suggest that malignant phenotypical changes associated with tumor invasion, metastasis and angiogenesis is associated with epigenetic alterations mediated by histone modification by LSD2.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 54, Wednesday Morning