Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Busan, Republic of Korea.
Cancer Lett. 2010 Aug 1;294(1):125-33. doi: 10.1016/j.canlet.2010.01.031. Epub 2010 Feb 25.
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.
磷脂酶 D (PLD) 已成为细胞生长信号转导中的关键因素。尽管关于 PLD 活性在细胞存活中的调节有广泛的信息，但调节癌症中 PLD 表达的信号机制仍知之甚少。在这里，我们研究了血小板衍生生长因子 (PDGF) 通过 Ras-ERK/PI3K-NFκB 信号级联增加 SK-BR3 乳腺癌细胞中 PLD1 但不增加 PLD2 的表达。这两个 NFκB 结合位点对于 PDGF 诱导的 PLD1 转录激活是功能上至关重要的。此外，使用 siRNA 耗尽 PLD1 可显著抑制 PDGF 诱导的基质金属蛋白酶-2 或 -9 的上调和乳腺癌细胞的侵袭。因此，我们提出 PDGF 通过 NFκB 信号通路诱导 PLD1 表达可能有助于致癌作用。
