title: Correlation between erythropoietin receptor(s) and estrogen and progesterone             receptor expression in different breast cancer cell lines.
abstract: Erythropoietin (EPO) receptor (EPOR) expression in breast cancer has been             shown to correlate with the expression of estrogen receptor (ESR) and progesterone             receptor (PGR) and to be associated with the response to tamoxifen in ESR+/PGR+             tumors but not in ESR- tumors. In addition, the correlation between EPOR and G protein-coupled             estrogen receptor 1 [GPER; also known as G protein-coupled receptor 30 (GPR30)]             has been reported, suggesting the prognostic potential of EPOR expression. Moreover,             the involvement of colony stimulating factor 2 receptor, β, low‑affinity (CSF2RB)             and ephrin type-B receptor 4 (EPHB4) as EPOR potential receptor partners in cancer             has been indicated. This study analyzed the correlation between the expression             of genes for EPO, EPOR, CSF2RB, EPHB4, ESR, PGR and GPER in the MCF-7, MDA-MB-361,             T-47D, MDA-MB-231, Hs578Bst, SKBR3, MCF-10A and Hs578T cell lines. The cell lines             were also treated with recombinant human EPO (rHuEPO) in order to determine its             ability to activate the Jak/STAT5, MAPK and PI3K signaling pathways and modify             cell growth characteristics. Expression analysis stratified the cell lines in             2 main clusters, hormone-dependent cell lines expressing ESR and PGR and a hormone-independent             cluster. A significant correlation was observed between the expression levels             of ESR and PGR and their expression was also associated with that of GPER. Furthermore,             the expression of GPER was associated with that of EPOR, suggesting the connection             between this orphan G protein and EPO signaling. A negative correlation between             EPOR and CSF2RB expression was observed, questioning the involvement of these             two receptors in the hetero-receptor formation. rHuEPO treatment only influenced             the hormone-independent cell lines, since only the MDA-MB-231, SKBR3 and Hs578T             cells responded to the treatment. The correlation between the expression of the             analyzed receptors suggests that the receptors may interact in order to activate             signaling pathways or to evade their inhibition. Therefore, breast cancer classification             upon ESR, PGR and human epidermal growth factor receptor 2 (HER2) may not be sufficient             for the selection of suitable treatment protocol. The expression of EPOR, GPER             and EPHB4 may be considered as additional classification factors.
authors: Institute of Biochemistry, Faculty of Medicine, University of                     Ljubljana, Ljubljana, Slovenia.
authors: Nina
authors: N
authors: Trošt
authors: Neli
authors: N
authors: Hevir
authors: Tea Lanišnik
authors: TL
authors: Rižner
authors: Nataša
authors: N
authors: Debeljak
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006801:Humans; D036224:Receptor, EphB4 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D036224:Receptor, EphB4; D018719:Erb-b2 Receptor Tyrosine Kinases; D017467:Receptors, Erythropoietin; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D011980:Receptors, Progesterone; C109584:GPER1 protein, human; C508053:ERBB2 protein, human