Oncostatin M induces the differentiation of breast cancer cells
Details
Publication Year 1998-01-05,Volume 75,Issue #1,Page 64-73
Journal Title
INTERNATIONAL JOURNAL OF CANCER
Publication Type
Journal Article
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 G(0)/G(1). After 6 days, there was a IO-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. (C) 1998 Wiley-Liss, Inc.
Publisher
WILEY-LISS
Keywords
GROWTH-FACTOR-RECEPTOR; LEUKEMIA-INHIBITORY FACTOR; COLONY-STIMULATING FACTOR; GENE-EXPRESSION; CARCINOMA CELLS; FACTOR-ALPHA; CYCLE PROGRESSION; ESTROGEN; CYTOKINE; INTERLEUKIN-6
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Creation Date: 1998-01-05 12:00:00
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