Platelet derived growth factor increases phospholipase D1 but not phospholipase D2 expression via NFkappaB signaling pathway and enhances invasion of breast cancer cells.
Phospholipase D (PLD) has emerged as a critical element in the cell growth signaling. Despite extensive information regarding the regulation of PLD activity in cell survival, the signaling mechanisms that regulate PLD expression in cancer remains poorly understood. Here we investigate that platelet derived growth factor (PDGF) increases PLD1 but not PLD2 expression via Ras-ERK/PI3K-NFkappaB signaling cascade in SK-BR3 breast cancer cells. The two NFkappaB-binding sites are functionally critical for transcriptional activation of PLD1 induced by PDGF. Furthermore, depletion of PLD1 using siRNA significantly abolished PDGF-induced upregulation of matrix metalloproteinase-2 or -9 and invasion of breast cancer cells. Thus, we propose that PDGF-induced PLD1 expression via NFkappaB signaling pathway might contribute to carcinogenesis.
Kang
Dong Woo
DW
Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Busan, Republic of Korea.
Min
Do Sik
do S
D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology*; D009361:Neoplasm Invasiveness; D010739:Phospholipase D / Q000172:deficiency / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
D017931:DNA Primers; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D008156:Luciferases; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9