Independently arising macrophage mutants dissociate growth factor-regulated survival and proliferation

Jeffrey W. Pollard, Claudia J. Morgan, Persio Dello Sbarba, Christina Cheers, E. Richard Stanley

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Analysis of a simian virus 40-immortalized colony-stimulating factor 1 (CSF-1) -dependent macrophage cell line (BAC1.2F5) and independently arising autonomous mutants derived from it (aut4A, aut4A.1, aut2A, and aut2A.1) revealed distinct phenotypes. The parental line, BAC1.2F5, is dependent on CSF-1 for survival and growth. Of the mutants derived from BAC1.2F5, aut4A has lost the requirement of CSF-1 for survival; aut4A.l (derived from aut4A) and aut2A grow in the absence of growth factor but proliferate more rapidly in its presence, and aut2A.1 (derived from aut2A) produces CSF-1 and proliferates as rapidly in the presence as in the absence of exogenous CSF-1, The separation of the CSF-1 requirement for survival and proliferation observed in aut4A is also observed in a temperature-sensitive (ts) mutant tsgrol. At the nonpermissive temperature, tsgrol cell proliferation is arrested, but the cells survive provided CSF-1 is present. The four cellular phenotypes observed - immortalization, loss of growth factor requirement for survival, loss of growth factor requirement for proliferation, and loss of growth factor-stimulated proliferation - indicate a divergence of the pathways of growth factor-regulated survival and proliferation and may represent phenotypes occurring at intermediate stages in tumor-cell progression.

Original languageEnglish (US)
Pages (from-to)1474-1478
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number4
DOIs
StatePublished - Jan 1 1991

Keywords

  • Autocrine
  • Cell survival
  • Colony-stimulating factor 1
  • Growth factor
  • Tumor progression

ASJC Scopus subject areas

  • General

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