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

Do Sik Min, Taeg Kyu Kwon, Won Sang Park, Jong Soo Chang, Seung Kiel Park, Bong Hyun Ahn, Zae Young Ryoo, Young Han Lee, Yeon Soo Lee, Duck Joo Rhie, Shin Lee Yoon, Sang June Hahn, Myuk Suk Kim, Yang Hyeok Jo

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Abstract

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.

Original languageEnglish
Pages (from-to)1641-1647
Number of pages7
JournalCarcinogenesis
Volume22
Issue number10
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Cancer Research

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    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. L., Hahn, S. J., Kim, M. S., & Jo, Y. H. (2001). Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts. Carcinogenesis, 22(10), 1641-1647. https://doi.org/10.1093/carcin/22.10.1641