TY - JOUR
T1 - Oncostatin M-specific receptor expression and function in regulating cell proliferation of normal and malignant mammary epithelial cells
AU - Liu, Jingwen
AU - Hadjokas, Nicholas
AU - Mosley, Brace
AU - Estrov, Zeev
AU - Spence, Michael J.
AU - Vestal, Robert E.
N1 - Funding Information:
We would like to thank Drs Philip M[ Wallace and Ingegerd Hellstrom at Bristol!Myers Squibb Pharmaceutical Research Institute for providing the breast cancer cell lines and human recombinant oncostatin M\ and Kristin Forcier for her excellent technical assistance[ This study was supported by the Department of Veterans of A}airs "O.ce of Research and Develop! ment\ Medical Research Service#\ by a grant "AIBS (071# from the United States Army Medical Research and Development Command\ and by the John O[ and Ester L[ Wallace Endowed Fund[
PY - 1998/4
Y1 - 1998/4
N2 - Oncostatin M (OSM) is a cytokine produced by activated T lymphocytes and macrophages, OSM is structurally and functionally related to leukaemia inhibitory factor (LIF), another cytokine in the interleukin 6 (IL-6) family. The biological activities of OSM are mediated through two types of receptor complexes, the LIF/OSM shared receptor (type I) and OSM-specific receptor (OSM-R, type II), which is composed of gp130 as a binding subunit and a newly identified affinity conversion subunit, OSM-Rβ. Previous research conducted in the authors' laboratory has shown that OSM inhibits the growth of several breast cancer cell lines. To investigate whether OSM has a similar effect in primary normal human mammary epithelial (HME) cells, the activity of OSM in HME cells derived from four donors was examined. OSM produced a dose-dependent inhibition of DNA synethesis in these cells. In order to determine the receptor subtypes mediating OSM activity in HME and breast cancer cells, flow cytometry analysis using anti-gp130mAb and anti-OSM-RβmAb was performed. In these studies, the authors were able to examine expressions of gp130 and OSM-Rβ. In addition, quantitative RT-PCR assays were conducted to measure expressions of the mRNAs of the subunits for type I and type II OSM receptor. The results show that HME cells and most breast cancer cell lines express both the type I and the type II OSM receptors. However, type II, OSM-specific receptors are expressed at a higher levels than type I, OSM/LIF shared receptors. Accordingly, we compared the growth regulatory activities of OSM with LIF in HME cells and in breast cancer cells. In contrast to the inhibitory activity of OSM, LIF stimulated the growth of breast cancer cells, whereas it had no effect on normal mammary epithelial cell growth. Together, these data suggest that OSM plays an inhibitory role in normal and malignant mammary epithelial cell growth in vitro. OSM activity is mediated by the OSM-specific receptor (type II), not by the OSM/LIF shared receptor.
AB - Oncostatin M (OSM) is a cytokine produced by activated T lymphocytes and macrophages, OSM is structurally and functionally related to leukaemia inhibitory factor (LIF), another cytokine in the interleukin 6 (IL-6) family. The biological activities of OSM are mediated through two types of receptor complexes, the LIF/OSM shared receptor (type I) and OSM-specific receptor (OSM-R, type II), which is composed of gp130 as a binding subunit and a newly identified affinity conversion subunit, OSM-Rβ. Previous research conducted in the authors' laboratory has shown that OSM inhibits the growth of several breast cancer cell lines. To investigate whether OSM has a similar effect in primary normal human mammary epithelial (HME) cells, the activity of OSM in HME cells derived from four donors was examined. OSM produced a dose-dependent inhibition of DNA synethesis in these cells. In order to determine the receptor subtypes mediating OSM activity in HME and breast cancer cells, flow cytometry analysis using anti-gp130mAb and anti-OSM-RβmAb was performed. In these studies, the authors were able to examine expressions of gp130 and OSM-Rβ. In addition, quantitative RT-PCR assays were conducted to measure expressions of the mRNAs of the subunits for type I and type II OSM receptor. The results show that HME cells and most breast cancer cell lines express both the type I and the type II OSM receptors. However, type II, OSM-specific receptors are expressed at a higher levels than type I, OSM/LIF shared receptors. Accordingly, we compared the growth regulatory activities of OSM with LIF in HME cells and in breast cancer cells. In contrast to the inhibitory activity of OSM, LIF stimulated the growth of breast cancer cells, whereas it had no effect on normal mammary epithelial cell growth. Together, these data suggest that OSM plays an inhibitory role in normal and malignant mammary epithelial cell growth in vitro. OSM activity is mediated by the OSM-specific receptor (type II), not by the OSM/LIF shared receptor.
KW - Cell proliferation
KW - Cytokine receptors
KW - Leukaemia inhibitor factor
KW - Oncostatin M
KW - gp130
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UR - http://www.scopus.com/inward/citedby.url?scp=0032055913&partnerID=8YFLogxK
U2 - 10.1006/cyto.1997.0283
DO - 10.1006/cyto.1997.0283
M3 - Article
C2 - 9617575
AN - SCOPUS:0032055913
SN - 1043-4666
VL - 10
SP - 295
EP - 302
JO - Cytokine
JF - Cytokine
IS - 4
ER -