Role of High-Affinity Oncostatin M Receptor in Prevention of Breast Cancer Cell Growth.
Annual rept. 1 Apr 95-31 Mar 96,
VETERANS ADMINISTRATION MEDICAL CENTER BOISE ID
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The biological activities of OM can be mediated by two different heterodimeric receptor complexes, the LIFOM shared receptor and the OM-specific receptor which is composed of gp130 and a newly identified signal transducing subunit. In this study, we have investigated the growth inhibitory mechanism of OM on breast cancer cells and the receptor subtype involved in OM action. Our data show that the growth inhibitory activity of OM is partially due to its functional antagonism of breast cancer mitogens including EGF, EGF-like growth factor, and bFGF. The proliferative activities of these growth factors were totally abolished by cotreatment of breast cancer cells with OM. EGF binding and the induction of EGF- receptor tyrosine phosphorylation were not affected by OM, suggesting that OM interferes with the mitogenic signal at steps distal to the EGF receptor. Examination of protooncogene expression demonstrated that OM down regulates the c-myc gene in growth-inhibited breast cancer cells. The biological effects reported herein are not shared by the OM-related cytokines IL-6, IL-11, or LIF as demonstrated by the inability of these proteins to inhibit growth or modulate c-myc gene expression in breast cancer cells. Furthermore, the 125OM binding to breast cancer cells can not be replaced by LIF suggesting a direct binding to OM specific receptor. Together these data suggest that the growth inhibitory activity is mediated predominantly through the OM-specific receptor, and activation of this receptor abrogates growth factors stimulation and down regulates the c-myc prooncogene.
- *PREVENTIVE MEDICINE
- *BREAST CANCER
- LASER INDUCED FLUORESCENCE
- AMINO ACIDS
- SCINTILLATION COUNTERS
- Medicine and Medical Research