Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor beta 1.
One of the more intriguing aspects of transforming growth factor beta 1 (TGF beta 1) is its ability to function as both a mitogenic factor for certain mesenchymal cells and a potent growth inhibitor of lymphoid, endothelial, and epithelial cells. Data are presented indicating that c-myc may play a pivotal role in both the mitogenic and antiproliferative actions of TGF beta 1. In agreement with previous studies using C3H/10T1/2 fibroblasts constitutively expressing an exogenous c-myc cDNA, we show that AKR-2B fibroblasts expressing a chimeric estrogen-inducible form of c-myc (mycER) are able to form colonies in soft agar in the presence of TGF beta 1 only when c-myc is activated by hormone. Whereas these findings support a synergistic role for c-myc in mitogenic responses to TGF beta 1, we also find that c-myc can antagonize the growth-inhibitory response to TGF beta 1. Mouse keratinocytes (BALB/MK), which are normally growth-arrested by TGF beta 1, are rendered insensitive to the growth-inhibitory effects of TGF beta 1 upon mycER activation. This ability of mycER activation to block TGF beta 1-induced growth arrest was found to occur only when the fusion protein was induced with hormone in the early part of G1. Addition of estradiol late in G1 had no suppressive effect on TGF beta 1-induced growth inhibition.
Alexandrow
M G
MG
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Kawabata
M
M
Aakre
M
M
Moses
H L
HL
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta