Oncostatin M induces the differentiation of breast cancer cells

Abstract

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 α (TGFα). 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. Int. J. Cancer 75:64–73, 1998.