Hyperactive autocrine loop mediated by a NDF-related factor in neoplastic hamster embryo fibroblasts expressing an activated cph oncogene

M. A. Avila, J. A. Velasco, C. Cho, Ruth Lupu, D. Wen, V. Notario

Research output: Contribution to journalArticle

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Abstract

We described previously the characterization of a novel oncogene, cph, activated in primary Syrian hamster embryo fibroblasts by exposure to 3-methylcholanthrene. The present report describes the participation in the neoplastic conversion of cph-expressing (81C39) hamster fibroblasts of a hyperactive autocrine loop involving a new differentiation factor [NDP]-like protein. The tyrosine phosphorylation of the p185(erbB-2) receptor in the human breast carcinoma MDA-MB-453 cells was stimulated by conditioned medium from neoplastic 81C39 cells. The extent of this stimulatory effect was much greater than that induced by conditioned medium from normal 84-3 hamster cells. The p185(erbB-2) tyrosine phosphorylation-stimulating activity was partially blocked by the heparin analogue pentosan polysulfate [PPS], a known antagonist of p185(erbB-2) ligands, and was partially purified from 81C39 conditioned medium by heparin-Se-pharose chromatography. The level of p185(erbB-2) tyrosine phosphorylation-stimulating activity in the heparin-Se-pharose fractions correlated directly with their content in NDP-like protein as immunodetected with an anti-rat NDF antibody. Consistently, the steady-state level of NDF-related mRNA was found to be four times greater in neoplastic 81C39 cells than in normal 84-3 cells. However, the levels of erbB-2 mRNA were similar in both cell types, while the expression of erbB-4 mRNA was upregulated in the neoplastic fibroblasts. The ability of 81C39 conditioned medium to stimulate protein tyrosine phosphorylation and to induce other PPS-sensitive growth responses on 81C39 cells themselves suggested the involvement of an autocrine loop in their neoplastic conversion. The participation of a NDF-related factor in this autocrine loop was confirmed by the ability of an anti-NDF antibody to block the mitogenic activity present in their own conditioned medium. The involvement of the cph oncogene in the upregulation of NDF-related expression was evidenced when cph-transformed NIH3T3 fibroblasts showed elevated levels of NDF-related mRNA, and their conditioned medium induced tyrosine phosphorylation on MDA-MB-453 cells, reproducing the effect of the medium from 81C39 hamster cells.

Original languageEnglish (US)
Pages (from-to)963-971
Number of pages9
JournalOncogene
Volume10
Issue number5
StatePublished - 1995
Externally publishedYes

Fingerprint

Oncogenes
Cricetinae
Embryonic Structures
Fibroblasts
Conditioned Culture Medium
Phosphorylation
Pentosan Sulfuric Polyester
Tyrosine
Heparin
Messenger RNA
ErbB-2 Receptor
Proteins
Methylcholanthrene
Mesocricetus
Chromatography
Anti-Idiotypic Antibodies
Up-Regulation
Breast Neoplasms
Ligands
Antibodies

Keywords

  • Cell proliferation
  • cph transformation
  • erbB-2 tyrosine kinase
  • Mitogenic factors
  • Neoplastic conversion

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Hyperactive autocrine loop mediated by a NDF-related factor in neoplastic hamster embryo fibroblasts expressing an activated cph oncogene. / Avila, M. A.; Velasco, J. A.; Cho, C.; Lupu, Ruth; Wen, D.; Notario, V.

In: Oncogene, Vol. 10, No. 5, 1995, p. 963-971.

Research output: Contribution to journalArticle

Avila, M. A. ; Velasco, J. A. ; Cho, C. ; Lupu, Ruth ; Wen, D. ; Notario, V. / Hyperactive autocrine loop mediated by a NDF-related factor in neoplastic hamster embryo fibroblasts expressing an activated cph oncogene. In: Oncogene. 1995 ; Vol. 10, No. 5. pp. 963-971.
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