Epidermal growth factor attenuates cell proliferation by down-regulating the transforming growth factor-beta receptor in the osteoblastic cell line MC3T3-E1.
We investigated the role of transforming growth factor beta 1 (TGF-beta 1) in growth regulation of the murine osteoblastic cell line, MC3T3-E1. We detected TGF-beta activity in the conditioned medium of MC3T3-E1 cells and its activity was increased by acid treatment of the bioassay system using CC1 64 cells. Northern blot analysis revealed the expression of TGF-beta 1 precursor messenger ribonucleic acid (mRNA). MC3T3-E1 cells possessed a single class of high affinity TGF-beta 1 receptor (2.8 x 10(4) sites per cell, Kd = 196 pM). Cross-linking studies revealed three specific TGF-beta receptors with molecular masses of 65, 95 and 280 kDa. Both TGF-beta and epidermal growth factor (EGF) stimulated [3H]-thymidine incorporation into cells. EGF decreased the number of TGF-beta receptor dose-dependently, and pretreatment of cells with 10 nM EGF attenuated cell growth by TGF-beta. All these data suggested that TGF-beta might be an autocrine growth factor in murine osteoblastic MC3T3-E1 cells and that EGF might modulate the growth of cells by down-regulating the TGF-beta receptor level.
Jikihara
H
H
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Ikegami
H
H
Sakata
M
M
Morishige
K
K
Fujita
Y
Y
Kurachi
H
H
Miyake
A
A
Tanizawa
O
O
Terakawa
N
N
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D014316:Tritium; D004815:Epidermal Growth Factor; D004247:DNA; D013936:Thymidine