Mitochondrial protein p26 BCL2 reduces growth factor requirements of NIH3T3 fibroblasts.
The BCL2 (B cell lymphoma/leukemia-2) proto-oncogene encodes a 26-kDa protein that has been localized to the inner mitochondrial membrane and that has been shown to enhance the survival of some types of hematopoietic cells. Here we show that NIH3T3 fibroblasts stably transfected with a BCL2 expression plasmid exhibit reduced dependence on competence-inducing growth factors (platelet-derived growth factor, PDGF; epidermal growth factor, EGF) for initiation of DNA synthesis. The importance of BCL2 for growth factor-induced proliferation of these cells was further confirmed by the useage of BCL2 antisense oligodeoxynucleotides. The mechanisms by which overexpression of p26 BCL2 contributes to fibroblast proliferation are unknown, but do not involve alterations in: (a) the production of inositol triphosphates (IP3), (b) PDGF-induced transient elevations in cytosolic Ca2+ ions, or (c) the activity of protein kinase C enzymes in these transfected cells. The results imply that changes in mitochondrial functions play an important role in the early stages of the cell cycle that render 3T3 cells competent to respond to the serum progression factors that stimulate entry into S-phase.
Reed
J C
JC
University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia 19104.
Talwar
H S
HS
Cuddy
M
M
Baffy
G
G
Williamson
J
J
Rapp
U R
UR
Fisher
G J
GJ
D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism*; D015870:Gene Expression; D007295:Inositol Phosphates / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection
D007295:Inositol Phosphates; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D002118:Calcium