Gene: the LIF and
oncostatin M (OSM) genes lie in tandem on chromosome 22q12, separated by 16 kb of genomic DNA. This close physical linkage suggests a close evolutionary relationship between LIF and OSM. The LIF gene has a size of 7.6 kb (including the flanking regions) and comprises 3 exons, 2 introns and an usually long 3'-untranslated region (3.2 kb).
mRNA: size: 4.2 kb.
Protein: a pleiotropic inflammatory cytokine. LIF is member of a family of cytokines including
interleukin-11 (IL-11),
interleukin-6 (IL-6),
oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1).
Cell lines:
- LIF is produced by MDA-MB-231 breast cancer cells (BCC) and stimulates proliferation of the estrogen-dependent T-47D and MCF-7, estrogen-independent SK-BR-3 and BT-20, and fresh BCC (Kellokumpu-Lehtinen P. et al., 1996; Estrov Z. et al., 1995).
- MDA-MB-231 and T-47D BCC were transiently transfected with a luciferase-reporter construct bearing a 666 bp fragment of the LIF promoter; in MDA-MB-231 (additionnally transfected with the progesterone receptor), luciferase activity was increased by the progesterone agonist medroxy-progesterone acetate (MPA), an effect inhibited by the progestin antagonist RU486. This effect of MPA was restricted to a 82 bp fragment of the LIF promoter, a region containing no classical progesterone response element (Bamberger A.-M. et al., 1998).
Tumors:
- LIF expression was observed in 78% of 50 human breast cancers and correlated with favorable biological features, i.e. low S-phase fraction (SPF) and diploidy. LIF receptor (LIFR) expression was observed in 80% of the tumors and correlated with the presence of
estrogen receptor (ER) and diploidy. Coexpression of LIF and LIFR was associated with diploidy and low SPF. LIF staining was primarily cytoplasmic whereas LIFR staining was cytoplasmic in the majority of cases and membranous in a minority of cases. The presence of LIFR in the primary tumor specimens correlated with the growth stimulation of tumor cells (derived from the same specimens) by exogenous LIF in methylcellulose colony assays (Dhingra K. et al., 1998).
