Differential expression of transforming growth factor-beta 1 (TGF-beta 1) receptors in murine myeloid cell lines transformed with oncogenes. Correlation with differential growth inhibition by TGF-beta 1.
Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic polypeptide hormone known to play an important role as a modulator of hematopoietic processes in human and murine cells. One of the characteristics of TGF-beta 1 is the ability to inhibit the growth of several cell types, including cells of the myeloid lineage. To study the mechanism by which TGF-beta 1 inhibits the growth of myeloid cells, we have used three murine myeloid cell lines, the parental interleukin-3-dependent 32D-123 cell line and two retrovirally infected interleukin-3-independent cell lines (32D-abl, 32D-src), all of which are growth inhibited by TGF-beta 1. Each of these oncogene-transfected cells expresses a greater number of TGF-beta 1 receptors than the parental cell line and responds to TGF-beta 1 with increased sensitivity; 32D and 32D-src cells are 2- and 58-fold more sensitive to TGF-beta 1 inhibition than the parental cell line (ED50 = 35 pM). Both 32D-abl- and 32D-src-transformed cell lines expressed higher levels of the 65- and 85-kDa TGF-beta 1 receptor species than did the parental cells. We observed a correlation between the greater sensitivity of 32D-src cells to TGF-beta 1 and the more rapid down-modulation and reappearance of cell surface TGF-beta 1 receptors on 32D-src cells. Thus, the level of TGF-beta 1 receptor expression and rate of reexpression both have a crucial regulatory effect on the functional activity of the TGF-beta 1 ligand.
Birchenall-Roberts
M C
MC
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201.
Falk
L A
LA
Kasper
J
J
Keller
J
J
Faltynek
C R
CR
Ruscetti
F W
FW
D000818:Animals; D001345:Autoradiography; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D009857:Oncogenes; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D003432:Cross-Linking Reagents; D007377:Interleukin-3; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta