Oncostatin M
(OSM)

???

Gene: the OSM and leukemia inhibitory factor (LIF) genes lie in tandem on chromosome 22q12, separated by 16 kb of genomic DNA. This close physical linkage suggests a close evolutionary relationship between OSM and LIF. Contains 3 exons and 2 introns and has a length of about 5 kb.
mRNA: size: ~2 kb. Contains an A+U rich region at the 3' untranslated end.
Protein: OSM is a heat- and acid-stable 28 kDa glycoprotein, originally identified by its ability to inhibit the replication of A375 melanoma and other tumor cells but not normal human fibroblasts. Nucleotide sequence of the OSM mRNA predicts a 252-aminoacid (aa) polypeptide with a 25-aa signal peptide.
OSM is member of a family of cytokines including interleukin-11 (Il-11), leukemia inhibitory factor (LIF), interleukin-6 (Il-6), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1).

Cell lines:
- OSM inhibited the growth of 7 (including MCF-7 and ZR-75-1) of 10 breast cancer cell (BCC) lines and down-regulated c-myc gene expression (Liu J. et al., 1997).

- OSM was shown to inhibit proliferation of H3922, a human BCC line derived from a ductal infiltrating carcinoma. Treatment of H3922 BCC with OSM for 72 h lowered the steady-state level of c-myc mRNA to 16% of that seen in control cells. Down-regulation of c-myc mRNA levels was both dose and time dependent. Results from nuclear run-off analysis and mRNA stability studies established that a major component of the observed OSM-induced down-regulation of c-myc mRNA occured at the transcriptional level. OSM treatment of H3922 cells reduced the abundance of actively transcribed c-myc mRNAs to approximately 25% of that observed in control cells. These data were supported by the finding that OSM did not significantly affect the half-life of c-myc mRNA in actinomycin-treated H3922 cells (Spence M.J. et al., 1997).

- The inhibition of BCC 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 (Douglas A.M. et al., 1998).

Tumors:

Douglas A.M. et al. (1998) Oncostatin M induces the differentiation of breast cancer cells. Int. J. Cancer 75, 64-73.
Giovannini M. et al. (1993) Tandem linkage of genes coding for leukemia inhibitory factor (LIF) and oncostatin M (OSM) on human chromosome 22. Cytogenet. Cell Genet. 64, 240-244.
Liu J. et al. (1997) Oncostatin M-specific receptor mediates inhibition of breast cancer cell growth and down-regulation of the c-myc proto-oncogene. Cell Growth & Differ. 8, 667-676.
Malik N. et al. (1989) Molecular cloning, sequence analysis, and functional expression of a novel growth regulator, oncostatin M. Mol. Cell. Biol. 9, 2847-2853.
Rose T.M. et al. (1993) The genes for oncostatin M (OSM) and leukemia inhibitory factor (LIF) are tightly linked on human chromosome 22. Genomics 17, 136-140.
Spence M.J. et al. (1997) Oncostatin M-mediated transcriptional suppression of the c-myc gene in breast cancer cells. Cancer Res. 57, 2223-2228.
Zarling J.M. et al. (1986) Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc. Natl. Acad. Sci USA 83, 9739-9743.

Leukemia inhibitory factor, interleukin-6, interleukin-11