Min D S, Kwon T K, Park W S, Chang J S, Park S K, Ahn B H, Ryoo Z Y, Lee Y H, Lee Y S, Rhie D J, Yoon S H, Hahn S J, Kim M S, Jo Y H
Department of Physiology, Department of Pathology and Department of Laboratory Animal Research, College of Medicine, The Catholic University of Korea, Seoul.
Carcinogenesis. 2001 Oct;22(10):1641-7. doi: 10.1093/carcin/22.10.1641.
Phospholipase D (PLD) has been suggested to play an important role in a variety of cellular functions. PLD activity has been shown to be significantly elevated in many tumours and transformed cells, suggesting the possibility that PLD might be involved in tumorigenesis. In this study, we have established stable cell lines overexpressing PLD1 and PLD2 from fibroblast cells. These cells, but not control cells, showed altered growth properties and anchorage-independent growth in soft agar. Both PLD1 and PLD2 also induced an up-regulation of the activity of matrix metalloprotease-9 as detected by zymograms. Furthermore, both PLD1 and PLD2 transformants, but not vector-transfectants, induced undifferentiated sarcoma when transplanted into nude mice. Both PLD1- and PLD2-mediated cell cycle distributions in stable cell lines revealed an increased fraction of cells in the S phase compared with control cells. Interestingly, the level of cyclin D3 protein, known as an activator of G(1) to S phase transition in the cell cycle, was aberrantly high in cells overexpressing PLD1 and PLD2 compared with control cells. These results suggest that overexpression of PLD isozymes may play an important role in neoplastic transformation.
磷脂酶D（PLD）被认为在多种细胞功能中发挥重要作用。在许多肿瘤和转化细胞中，PLD活性已被证明显著升高，这表明PLD可能参与肿瘤发生。在本研究中，我们从成纤维细胞建立了过表达PLD1和PLD2的稳定细胞系。这些细胞而非对照细胞，在软琼脂中表现出改变的生长特性和不依赖贴壁的生长。通过酶谱分析检测到，PLD1和PLD2均诱导基质金属蛋白酶-9活性上调。此外，当将PLD1和PLD2转化体而非载体转染体移植到裸鼠中时，会诱导未分化肉瘤。与对照细胞相比，PLD1和PLD2介导的稳定细胞系中的细胞周期分布显示S期细胞比例增加。有趣的是，与对照细胞相比，在过表达PLD1和PLD2的细胞中，细胞周期中已知的G（1）期到S期转变激活剂细胞周期蛋白D3的水平异常高。这些结果表明，PLD同工酶的过表达可能在肿瘤转化中起重要作用。
