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

Citation
Ds. Min et al., Neoplastic transformation and tumorigenesis associated with overexpressionof phospholipase D isozymes in cultured murine fibroblasts, CARCINOGENE, 22(10), 2001, pp. 1641-1647
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
0143-3334 → ACNP
Volume
22
Issue
10
Year of publication
2001
Pages
1641 - 1647
Database
ISI
SICI code
0143-3334(200110)22:10<1641:NTATAW>2.0.ZU;2-5
Abstract
Phospholipase D (PLD) has been suggested to play an important role in a var iety 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 establ ished stable cell lines overexpressing PLD1 and PLD2 from fibroblast cells. These cells, but not control cells, showed altered growth properties and a nchorage-independent growth in soft agar. Both PLD1 and PLD2 also induced a n up-regulation of the activity of matrix metalloprotease-9 as detected by zymograms. Furthermore, both PLD1 and PLD2 transformants, but not vector-tr ansfectants, induced undifferentiated sarcoma when transplanted into nude m ice. Both PLD1- and PLD2-mediated cell cycle distributions in stable cell l ines revealed an increased fraction of cells in the S phase compared with c ontrol cells. Interestingly, the level of cyclin D3 protein, known as an ac tivator of Gl to S phase transition in the cell cycle, was aberrantly high in cells overexpressing PLD1 and PLD2 compared with control cells. These re sults suggest that overexpression of PLD isozymes may play an important rol e in neoplastic transformation.