Role of High-Affinity Oncostatin M Receptor in Prevention of Breast Cancer Cell Growth.
Final rept. 9 May 94-29 Sep 98
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Oncostatin M OM, a T cell, and macrophages derived cytokine, has profound effects on malignant and normal mammary epithelial cells. In this study, we have investigated the growth inhibitory mechanism of OM on breast cancer cells and the receptor subtype involved in OM action. We show that OM inhibits the growth of a variety of breast cancer cell lines. 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. Examination of proto oncogene expression demonstrated that OM down regulates the c-myc gene in growth- inhibited breast cancer cells. Interestingly, we also found that the transcription of p53 gene was inhibited by OM in breast cancer cells that contain the mutated p53 gene, but OM had no effect on p53 gene in cells contain the normal p53 gene. The biological effects reported herein are not shared by the OM-related cytokines IL-6, IL-11, or LIF. Our data suggest that the biological functions of OM in breast cancer is mediated predominantly through the OM-specific receptor, and activation of this receptor abrogates growth factors stimulation and down regulates the c-myc protooncogene.
- Anatomy and Physiology
- Medicine and Medical Research