Active c-erbB-2 induces short-term growth of FDC-P2 cells after IL-3 depletion.
A retroviral expression vector carrying the c-erbB-2 gene was introduced into the FDC-P2 myeloid cell line, which is absolutely dependent on interleukin-3 (IL-3) for proliferation and survival. Since the c-erbB-2 protein appears to be the receptor of an as yet unidentified growth factor, epidermal growth factor receptor (EGFR) was used as a control of a ligand-dependent receptor. FDC-P2 cells expressing normal c-erbB-2 were unable to grow without IL-3 stimulation. The c-erbB-2 protein in these cells was under-phosphorylated on tyrosine residues in vivo. On the contrary, the active c-erbB-2 protein, in which Val-659 was replaced by Glu in the transmembrane domain, and EGF-stimulated EGFR showed significant levels of tyrosine phosphorylation in vivo. These active proteins could promote short-term growth of FDC-P2 cells without IL-3 stimulation, though not indefinitely. These findings suggested that immortalization of this factor-dependent cell line requires an additional oncogenic promoting process(es).
Department of Oncology, University of Tokyo, Japan.
B
B
Wongsasant
S
S
Matsuda
T
T
Yamamoto
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D014162:Transfection
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors; D007377:Interleukin-3; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases