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Oncostatin M induces the differentiation of breast cancer cells
Author(s) -
Douglas Andrea M.,
Grant Susan L.,
Gross Geraldine A.,
Clouston David R.,
Sutherland Robert L.,
Begley C. Glenn
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980105)75:1<64::aid-ijc11>3.0.co;2-d
Subject(s) - oncostatin m , clonogenic assay , cell culture , cell growth , cancer cell , biology , receptor , cell cycle , estrogen receptor , endocrinology , cancer research , cell , medicine , microbiology and biotechnology , cytokine , breast cancer , cancer , immunology , biochemistry , interleukin 6 , genetics
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 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.© 1998 Wiley‐Liss, Inc.