Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody

Maryann B. Flick, Eva Sapi, Peter L. Perrotta, M. Grey Maher, Ruth Halaban, Darryl Carter, Barry M. Kacinski

Research output: Contribution to journalArticle

Abstract

The macrophage colony stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, plays an important role in regulating the normal proliferation and differentiation of macrophages and trophoblasts. However, the abnormal expression of CSF-1R transcripts and protein by human breast carcinomas has been shown to correlate with advanced stage and poor prognosis. Ligand activated CSF-1R dimers transphosphorylate several tyrosines in their cytoplasmic domains which provide recognition sites for various effector proteins in multiple signal transduction pathways. In cells transformed by the c-fms oncogene, one of the major CSF-1R phosphotyrosines, pTyr723 is important for phenotypic expression of anchorage-independent growth and metastasis. In order to investigate the relationship between receptor activation/phosphorylation and cellular phenotypes in vitro and in vivo, we prepared a CSF-1R phosphorylation-state specific antibody raised against a specific phosphopeptide of CSF-1R, which included phosphorylated tyrosine 723. On immunoblots of lysates from cells expressing CSF-1R, this antibody recognizes phosphorylated CSF-1R in CSF-1 stimulated cells but not in unstimulated cells. As an immunohistochemical reagent, this antibody stained 52% of invasive human breast tumors (72% of CSF-1R positive cases) in a sample of 114 cases and 38% of carcinoma in situ. This data represents the first direct evidence of in vivo phosphorylation of CSF-1R in human breast carcinomas.

Original languageEnglish (US)
Pages (from-to)2553-2561
Number of pages9
JournalOncogene
Volume14
Issue number21
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Breast carcinoma
  • c-fms proto-oncogene
  • Immunohistochemistry
  • Phosphotyrosine
  • Tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody'. Together they form a unique fingerprint.

  • Cite this

    Flick, M. B., Sapi, E., Perrotta, P. L., Maher, M. G., Halaban, R., Carter, D., & Kacinski, B. M. (1997). Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody. Oncogene, 14(21), 2553-2561. https://doi.org/10.1038/sj.onc.1201092