Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts

• Published in: Carcinogenesis (New York) 2001-10, Vol.22 (10), p.1641-1647
• Main Authors: Min, Do Sik, Kwon, Taeg Kyu, Park, Won-Sang, Chang, Jong-Soo, Park, Seung-Kiel, Ahn, Bong-Hyun, Ryoo, Zae-Young, Lee, Young Han, Lee, Yeon Soo, Rhie, Duck-Joo, Yoon, Shin-Hee, Hahn, Sang June, Kim, Myung-Suk, Jo, Yang-Hyeok
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cdk; Cell Cycle; Cell Division; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cells, Cultured; Cyclin D3; cyclin-dependent kinase; Cyclin-Dependent Kinases - metabolism; Cyclins - metabolism; Female; Fibroblasts - enzymology; Fundamental and applied biological sciences. Psychology; Humans; Immunoenzyme Techniques; LPA; lysophosphatidic acid; matrix metalloprotease; Matrix Metalloproteinases - metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; MMP; Molecular and cellular biology; phosphatidic acid; phospholipase D; Phospholipase D - genetics; Phospholipase D - metabolism; PLD; Sarcoma, Experimental - enzymology; Sarcoma, Experimental - pathology
• ISSN: 0143-3334; 1460-2180; 1460-2180
• 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 G1 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.