Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts.
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.
Min
D S
DS
Department of Physiology, Department of Pathology and Department of Laboratory Animal Research, College of Medicine, The Catholic University of Korea, Seoul. dsmin@cmc.cuk.ac.kr
Kwon
T K
TK
Park
W S
WS
Chang
J S
JS
Park
S K
SK
Ahn
B H
BH
Ryoo
Z Y
ZY
Lee
Y H
YH
Lee
Y S
YS
Rhie
D J
DJ
Yoon
S H
SH
Hahn
S J
SJ
Kim
M S
MS
Jo
Y H
YH
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D056743:Cyclin D3; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D012513:Sarcoma, Experimental / Q000201:enzymology* / Q000473:pathology
C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D018844:Cyclin-Dependent Kinases; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D020782:Matrix Metalloproteinases