Transduction of human colony-stimulating factor-1 (CSF-1) receptor into interleukin-3-dependent mouse myeloid cells induces both CSF-1-dependent and factor-independent growth.
A retroviral vector encoding the receptor for human colony-stimulating factor-1 (CSF-1) was introduced into murine myeloid FDC-P1 cells which require interleukin-3 (IL-3) for their proliferation and survival in culture. Cells expressing the CSF-1 receptor (CSF-1R), selected by fluorescence-activated cell sorting in the continued presence of murine IL-3, formed colonies in semisolid medium and were able to proliferate continuously in liquid cultures containing human recombinant CSF-1. Thus, although they do not synthesize endogenous murine CSF-1R, FDC-P1 cells express the downstream components of the CSF-1 mitogenic pathway necessary for its signal-response coupling. After receptor transduction, slowly proliferating factor-independent variants that produced neither CSF-1 nor growth factors able to support the proliferation of parental FDC-P1 cells also arose. When the human CSF-1R was expressed in FDC-P1 cells under the control of an inducible metallothionein promoter, the frequencies of both CSF-1-responsive and factor-independent variants increased after heavy-metal treatment. In addition, a monoclonal antibody to human CSF-1R arrested colony formation by both the CSF-1-dependent and factor-independent cells but did not affect their growth in response to IL-3. Therefore, the induction of both the CSF-1-dependent and factor-independent phenotypes depended on expression of the transduced human CSF-1R.
Kato
J Y
JY
Howard Hughes Medical Institute, Memphis, Tennessee.
Roussel
M F
MF
Ashmun
R A
RA
Sherr
C J
CJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005822:Genetic Vectors; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D014161:Transduction, Genetic
D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor