title: Epidermal growth factor attenuates cell proliferation by down-regulating the transforming growth factor-beta receptor in the osteoblastic cell line MC3T3-E1.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Jikihara
authors.forename: H
authors.initials: H
authors.lastname: Ikegami
authors.forename: M
authors.initials: M
authors.lastname: Sakata
authors.forename: K
authors.initials: K
authors.lastname: Morishige
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.forename: H
authors.initials: H
authors.lastname: Kurachi
authors.forename: A
authors.initials: A
authors.lastname: Miyake
authors.forename: O
authors.initials: O
authors.lastname: Tanizawa
authors.forename: N
authors.initials: N
authors.lastname: Terakawa
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D014316:Tritium; D004815:Epidermal Growth Factor; D004247:DNA; D013936:Thymidine