Oncostatin M induces the differentiation of breast cancer cells

Int J Cancer. 1998 Jan 5;75(1):64-73. doi: 10.1002/(sici)1097-0215(19980105)75:1<64::aid-ijc11>3.0.co;2-d.


We have recently described the action of Oncostatin M (OSM) to inhibit the proliferation of breast cancer cells. In this study we examined the action of OSM on 2 breast cancer cell lines to further characterize the nature of OSM inhibition of cellular proliferation. Treatment with OSM for 6 days resulted in an approximately 2- to 5-fold decrease in cell number, which was independent of estrogen receptor status. Consistent with this, colony formation was reduced to approximately 50% when cells were exposed to OSM in primary agar cultures. Clonogenicity was further inhibited following 7 days treatment with OSM in monolayer cultures: the total number of clonogenic cells was suppressed approximately 10-fold. Analysis of cell cycle status in OSM-treated cells demonstrated a 40% reduction in the proportion of cells in S phase within 12 hr, with an increase in cells in G0/G1. After 6 days, there was a 10-fold reduction in the absolute number of cells in S phase in OSM-treated cultures. These changes were associated with striking changes in cellular morphology, including disruption of intercellular junctions and the production of lipid droplets. There was a 5-fold increase of c-fos and c-myc mRNA within 30 min of commencing treatment with OSM. In addition, in the ER positive cells there was a decrease in ER mRNA (evident within approximately 2 hr) and ER protein expression following treatment with OSM. Conversely, there was a 5-fold increase in epidermal growth factor receptor (EGFR) mRNA within 4 hr, and a 2.5-fold rise in mRNA for transforming growth factor alpha (TGF alpha). Thus, the inhibition of breast cancer cells by OSM was associated with decreased clonogenicity, a decrease in S phase cells and a variety of phenotypic changes, all consistent with the induction of differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / pathology*
  • Cell Count / drug effects
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects
  • Cyclins / drug effects
  • Cyclins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Genes, fos / drug effects
  • Genes, myc / drug effects
  • Growth Inhibitors / pharmacology*
  • Growth Substances / metabolism
  • Humans
  • Oncostatin M
  • Peptides / pharmacology*
  • RNA, Messenger / metabolism
  • Receptors, Growth Factor / drug effects
  • Receptors, Growth Factor / metabolism
  • STAT3 Transcription Factor
  • Trans-Activators*
  • Tumor Cells, Cultured / drug effects
  • Tumor Stem Cell Assay


  • Antineoplastic Agents
  • Cyclins
  • DNA-Binding Proteins
  • Growth Inhibitors
  • Growth Substances
  • OSM protein, human
  • Peptides
  • RNA, Messenger
  • Receptors, Growth Factor
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Oncostatin M