Carcinogenesis, Vol. 22, No. 10, 1641-1647,
October 2001
© 2001 Oxford University Press
CANCER BIOLOGY |
Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts
Department of Physiology,
1 Department of Pathology and
2 Department of Laboratory Animal Research, College of Medicine, The Catholic University of Korea, Seoul, 137-701,
3 Department of Immunology, College of Medicine, Keimyung University, Taegu,
4 Department of Life Science, Daejin University, Pochon-gun, Kyeonggido,
5 Department of Biochemistry, College of Medicine, Chungnam National University, Taejon and
6 Department of Biochemistry & Molecular Biology, College of Medicine, Yeungnam University, Taegu, Korea
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.
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