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Recombinant human erythropoietin alters gene expression and stimulates proliferation of MCF-7 breast cancer cells.

Trost N, Stepisnik T, Berne S, Pucer A, Petan T, Komel R, Debeljak N - Radiol Oncol (2013)

Bottom Line: Three different isoforms of erythropoietin receptor (EPOR) have been reported, the soluble (EPOR-S) and truncated (EPOR-T) forms acting antagonistically to the functional EPOR.Gene expression analysis showed activation of EGR1 and FOS, confirming the functionality of EPOR. rHuEPO treatment also slightly increased the expression of the functional EPOR isoform, which, however, persisted throughout the 10 weeks of treatment.The expression levels of EPOR-T were not influenced.

View Article: PubMed Central - PubMed

Affiliation: Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia.

ABSTRACT

Background: Functional erythropoietin (EPO) signaling is not specific only to erythroid lineages and has been confirmed in several solid tumors, including breast. Three different isoforms of erythropoietin receptor (EPOR) have been reported, the soluble (EPOR-S) and truncated (EPOR-T) forms acting antagonistically to the functional EPOR. In this study, we investigated the effect of human recombinant erythropoietin (rHuEPO) on cell proliferation, early gene response and the expression of EPOR isoforms in the MCF-7 breast cancer cell line.

Materials and methods: The MCF-7 cells were cultured with or without rHuEPO for 72 h or 10 weeks and assessed for their growth characteristics, expression of early response genes and different EPOR isoforms. The expression profile of EPOR and EPOR-T was determined in a range of breast cancer cell lines and compared with their invasive properties.

Results: MCF-7 cell proliferation after rHuEPO treatment was dependent on the time of treatment and the concentration used. High rHuEPO concentrations (40 U/ml) stimulated cell proliferation independently of a preceding long-term exposure of MCF-7 cells to rHuEPO, while lower concentrations increased MCF-7 proliferation only after 10 weeks of treatment. Gene expression analysis showed activation of EGR1 and FOS, confirming the functionality of EPOR. rHuEPO treatment also slightly increased the expression of the functional EPOR isoform, which, however, persisted throughout the 10 weeks of treatment. The expression levels of EPOR-T were not influenced. There were no correlations between EPOR expression and the invasiveness of MCF-7, MDA-MB-231, Hs578T, Hs578Bst, SKBR3, T-47D and MCF-10A cell lines.

Conclusions: rHuEPO modulates MCF-7 cell proliferation in time- and concentration-dependent manner. We confirmed EGR1, FOS and EPOR as transcription targets of the EPO-EPOR signaling loop, but could not correlate the expression of different EPOR isoforms with the invasiveness of breast cancer cell lines.

No MeSH data available.


Related in: MedlinePlus

Expression of EPOR isoforms in different breast cancer cell lines; expression of functional EPOR (red); expression of truncated form of EPOR-T (blue). Cell lines differ in the level of invasiveness with MCF-10A cell line being the least invasive and Hs578T cell line being the most invasive (Table 1). Error bars represent standard deviations (SD) of the relative expression values determined in triplicate samples.
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f5-rado-47-04-382: Expression of EPOR isoforms in different breast cancer cell lines; expression of functional EPOR (red); expression of truncated form of EPOR-T (blue). Cell lines differ in the level of invasiveness with MCF-10A cell line being the least invasive and Hs578T cell line being the most invasive (Table 1). Error bars represent standard deviations (SD) of the relative expression values determined in triplicate samples.

Mentions: The expression of EPOR isoforms was paralleled with the invasiveness of cancer and epithelial-like breast cell lines included in the current study (Table 1). We found no association between the expression of EPOR (EPOR or EPOR-T) and the breast cell invasiveness. There were no significant differences in the level of EPOR expression between cell lines and its expression in a particular cell line did not correlate with its invasiveness, ESR, PGR or HER2 status (Figure 5).


Recombinant human erythropoietin alters gene expression and stimulates proliferation of MCF-7 breast cancer cells.

Trost N, Stepisnik T, Berne S, Pucer A, Petan T, Komel R, Debeljak N - Radiol Oncol (2013)

Expression of EPOR isoforms in different breast cancer cell lines; expression of functional EPOR (red); expression of truncated form of EPOR-T (blue). Cell lines differ in the level of invasiveness with MCF-10A cell line being the least invasive and Hs578T cell line being the most invasive (Table 1). Error bars represent standard deviations (SD) of the relative expression values determined in triplicate samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3814284&req=5

f5-rado-47-04-382: Expression of EPOR isoforms in different breast cancer cell lines; expression of functional EPOR (red); expression of truncated form of EPOR-T (blue). Cell lines differ in the level of invasiveness with MCF-10A cell line being the least invasive and Hs578T cell line being the most invasive (Table 1). Error bars represent standard deviations (SD) of the relative expression values determined in triplicate samples.
Mentions: The expression of EPOR isoforms was paralleled with the invasiveness of cancer and epithelial-like breast cell lines included in the current study (Table 1). We found no association between the expression of EPOR (EPOR or EPOR-T) and the breast cell invasiveness. There were no significant differences in the level of EPOR expression between cell lines and its expression in a particular cell line did not correlate with its invasiveness, ESR, PGR or HER2 status (Figure 5).

Bottom Line: Three different isoforms of erythropoietin receptor (EPOR) have been reported, the soluble (EPOR-S) and truncated (EPOR-T) forms acting antagonistically to the functional EPOR.Gene expression analysis showed activation of EGR1 and FOS, confirming the functionality of EPOR. rHuEPO treatment also slightly increased the expression of the functional EPOR isoform, which, however, persisted throughout the 10 weeks of treatment.The expression levels of EPOR-T were not influenced.

View Article: PubMed Central - PubMed

Affiliation: Center for Functional Genomics and Bio-chips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia.

ABSTRACT

Background: Functional erythropoietin (EPO) signaling is not specific only to erythroid lineages and has been confirmed in several solid tumors, including breast. Three different isoforms of erythropoietin receptor (EPOR) have been reported, the soluble (EPOR-S) and truncated (EPOR-T) forms acting antagonistically to the functional EPOR. In this study, we investigated the effect of human recombinant erythropoietin (rHuEPO) on cell proliferation, early gene response and the expression of EPOR isoforms in the MCF-7 breast cancer cell line.

Materials and methods: The MCF-7 cells were cultured with or without rHuEPO for 72 h or 10 weeks and assessed for their growth characteristics, expression of early response genes and different EPOR isoforms. The expression profile of EPOR and EPOR-T was determined in a range of breast cancer cell lines and compared with their invasive properties.

Results: MCF-7 cell proliferation after rHuEPO treatment was dependent on the time of treatment and the concentration used. High rHuEPO concentrations (40 U/ml) stimulated cell proliferation independently of a preceding long-term exposure of MCF-7 cells to rHuEPO, while lower concentrations increased MCF-7 proliferation only after 10 weeks of treatment. Gene expression analysis showed activation of EGR1 and FOS, confirming the functionality of EPOR. rHuEPO treatment also slightly increased the expression of the functional EPOR isoform, which, however, persisted throughout the 10 weeks of treatment. The expression levels of EPOR-T were not influenced. There were no correlations between EPOR expression and the invasiveness of MCF-7, MDA-MB-231, Hs578T, Hs578Bst, SKBR3, T-47D and MCF-10A cell lines.

Conclusions: rHuEPO modulates MCF-7 cell proliferation in time- and concentration-dependent manner. We confirmed EGR1, FOS and EPOR as transcription targets of the EPO-EPOR signaling loop, but could not correlate the expression of different EPOR isoforms with the invasiveness of breast cancer cell lines.

No MeSH data available.


Related in: MedlinePlus