The oncostatin M receptor/gp130 ligand murine oncostatin M induces apoptosis in adrenocortical Y-1 tumor cells.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: BioScientifica Country of Publication: England NLM ID: 0375363 Publication Model: Print Cited Medium: Print ISSN: 0022-0795 (Print) Linking ISSN: 00220795 NLM ISO Abbreviation: J Endocrinol Subsets: MEDLINE
    • Publication Information:
      Publication: Jan. 2011- : Bristol, UK : BioScientifica
      Original Publication: Bristol, UK : Society for Endocrinology
    • Subject Terms:
      Proto-Oncogene Proteins*; Adrenal Cortex Neoplasms/*drug therapy ; Antigens, CD/*therapeutic use ; Apoptosis/*drug effects ; Membrane Glycoproteins/*therapeutic use ; Peptides/*metabolism; Adrenal Cortex Neoplasms/metabolism ; Amino Acid Chloromethyl Ketones/pharmacology ; Animals ; Antigens, CD/metabolism ; Caspase Inhibitors ; Caspases/metabolism ; Cell Line, Tumor ; Cytokine Receptor gp130 ; Janus Kinase 2 ; Membrane Glycoproteins/metabolism ; Mice ; Oncostatin M ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Protein-Tyrosine Kinases/metabolism ; Signal Transduction/drug effects ; Tyrphostins/pharmacology
    • Abstract:
      The effects of murine oncostatin M (mOSM) are specifically mediated by the heterodimeric oncostatin M receptor (OSMR)/gp130 receptor complex. In the current study we demonstrate that murine adrenocortical Y-1 tumor cells express the OSMR/gp130 complex. Incubation of Y-1 cells with 1 and 10 ng/ml mOSM induces cell death due to specific induction of apoptosis. Western blot analysis of Y-1 cells incubated with mOSM for 24 h revealed caspase-3 cleavage and poly(ADP-ribase) polymerase (PARP) cleavage. In a proliferation assay system, incubation of Y-1 cells with 0.01, 0.1, 1 and 10 ng/ml mOSM for 24 h resulted in a decrease in cell numbers to 99+/-2%, 84+/-9%, 50+/-7% and 43+/-5% respectively of untreated control (defined as 100%). Pretreatment of Y-1 cells with the Jak2 inhibitor AG490 (100 microM) rescued Y-1 cells from OSM-induced (10 ng/ml) cell death. Similarly, pretreatment of Y-1 cells with the general caspase inhibitor Z-VAD-FMK (42 microM) rescued Y-1 cells from OSM-induced (10 ng/ml) cell death. In summary, we show that adrenocortical Y-1 tumor cells express the OSMR/gp130 complex and that mOSM induces the Jak-STAT signaling cascade in these cells. Murine OSM in a dose-dependent manner induces apoptosis in adrenocortical Y-1 tumor cells. Apoptosis was demonstrated by caspase-3 cleavage and PARP cleavage. Rescue of Y-1 cells from mOSM-induced apoptosis by the Jak2 inhibitor, AG490, and the general caspase inhibitor, Z-VAD-FMK, demonstrates Jak activation and subsequent caspase activation to be essential for mOSM-induced apoptosis in adrenocortical Y-1 tumor cells. The putative role of OSM as an immunotherapeutic agent in human adrenocortical cancer remains to be elucidated.
    • Accession Number:
      0 (Amino Acid Chloromethyl Ketones)
      0 (Antigens, CD)
      0 (Caspase Inhibitors)
      0 (Il6st protein, mouse)
      0 (Membrane Glycoproteins)
      0 (OSM protein, human)
      0 (Osm protein, mouse)
      0 (Peptides)
      0 (Proto-Oncogene Proteins)
      0 (Tyrphostins)
      0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
      0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
      106956-32-5 (Oncostatin M)
      133483-10-0 (Cytokine Receptor gp130)
      EC 2.7.10.1 (Protein-Tyrosine Kinases)
      EC 2.7.10.2 (JAK2 protein, human)
      EC 2.7.10.2 (Jak2 protein, mouse)
      EC 2.7.10.2 (Janus Kinase 2)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20040312 Date Completed: 20040527 Latest Revision: 20190709
    • Publication Date:
      20250114
    • Accession Number:
      10.1677/joe.0.1800479
    • Accession Number:
      15012602