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Contrasting effect of recombinant human erythropoietin on breast cancer cell response to cisplatin induced cytotoxicity.

Trost N, Juvan P, Sersa G, Debeljak N - Radiol Oncol (2012)

Bottom Line: Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression.On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(-) status.The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment.

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: Human recombinant erythropoietin (rHuEpo) that is used for the treatment of the chemotherapy-induced anaemia in cancer patients was shown to cause detrimental effects on the course of disease due to increased adverse events inflicting patient's survival, potentially related to rHuEpo-induced cancer progression. In this study, we elucidate the effect of rHuEpo administration on breast cancer cell proliferation and gene expression after cisplatin (cDDP) induced cytotoxicity.

Materials and methods: Two breast carcinoma models, MCF-7 and MDA-MB-231 cell lines, were used differing in oestrogen (ER) and progesterone (PR) receptors and p53 status. Cells were cultured with or without rHuEpo for 24 h or 9 weeks and their growth characteristics after cDDP treatment were assessed together with expression of genes involved in the p53-signaling pathway.

Results: Short-term exposure of breast cancer cells to rHuEpo lowers their proliferation and reduces cDDP cytotoxic potency. In contrast, long-term exposure of MCF-7 cells to rHuEpo increases proliferation and predisposes MCF-7 cells to cDDP cytotoxicity, but has no effect on MDA-MB-231 cells. MDA-MB-231 cells show altered level of ERK phosphorylation, indicating involvement of MAPK signalling pathway. Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression.

Conclusions: Proliferation and survival characteristics of MCF-7 cells are reversely modulated by the length of the rHuEpo exposure. On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(-) status. The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment.

No MeSH data available.


Related in: MedlinePlus

Surviving fraction of short (red line, A and C) and long-term (red line, B and D) rHuEpo treated cells after exposure to cDDP: (A and B) MCF-7; (C and D) MDA-MB-231 cell line. Asterisk (*) denotes statistical significant differences for Type I error α = 0.05.
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f4-rado-46-03-213: Surviving fraction of short (red line, A and C) and long-term (red line, B and D) rHuEpo treated cells after exposure to cDDP: (A and B) MCF-7; (C and D) MDA-MB-231 cell line. Asterisk (*) denotes statistical significant differences for Type I error α = 0.05.

Mentions: Clonogenic assays confirmed protective effect of short-term rHuEpo treatment for the MCF-7 cell response to cDDP cytotoxicity (Figure 4A), while they exposed sensitizing effect for MDA-MB-231 cells (Figure 4C). Long term exposure of cells to EPO predisposed MCF-7 cells to CDDP cytotoxicity (Figure 4B) but not the MDA-MB-231 cells (Figure 4D), as shown by WST-1.


Contrasting effect of recombinant human erythropoietin on breast cancer cell response to cisplatin induced cytotoxicity.

Trost N, Juvan P, Sersa G, Debeljak N - Radiol Oncol (2012)

Surviving fraction of short (red line, A and C) and long-term (red line, B and D) rHuEpo treated cells after exposure to cDDP: (A and B) MCF-7; (C and D) MDA-MB-231 cell line. Asterisk (*) denotes statistical significant differences for Type I error α = 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472952&req=5

f4-rado-46-03-213: Surviving fraction of short (red line, A and C) and long-term (red line, B and D) rHuEpo treated cells after exposure to cDDP: (A and B) MCF-7; (C and D) MDA-MB-231 cell line. Asterisk (*) denotes statistical significant differences for Type I error α = 0.05.
Mentions: Clonogenic assays confirmed protective effect of short-term rHuEpo treatment for the MCF-7 cell response to cDDP cytotoxicity (Figure 4A), while they exposed sensitizing effect for MDA-MB-231 cells (Figure 4C). Long term exposure of cells to EPO predisposed MCF-7 cells to CDDP cytotoxicity (Figure 4B) but not the MDA-MB-231 cells (Figure 4D), as shown by WST-1.

Bottom Line: Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression.On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(-) status.The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment.

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: Human recombinant erythropoietin (rHuEpo) that is used for the treatment of the chemotherapy-induced anaemia in cancer patients was shown to cause detrimental effects on the course of disease due to increased adverse events inflicting patient's survival, potentially related to rHuEpo-induced cancer progression. In this study, we elucidate the effect of rHuEpo administration on breast cancer cell proliferation and gene expression after cisplatin (cDDP) induced cytotoxicity.

Materials and methods: Two breast carcinoma models, MCF-7 and MDA-MB-231 cell lines, were used differing in oestrogen (ER) and progesterone (PR) receptors and p53 status. Cells were cultured with or without rHuEpo for 24 h or 9 weeks and their growth characteristics after cDDP treatment were assessed together with expression of genes involved in the p53-signaling pathway.

Results: Short-term exposure of breast cancer cells to rHuEpo lowers their proliferation and reduces cDDP cytotoxic potency. In contrast, long-term exposure of MCF-7 cells to rHuEpo increases proliferation and predisposes MCF-7 cells to cDDP cytotoxicity, but has no effect on MDA-MB-231 cells. MDA-MB-231 cells show altered level of ERK phosphorylation, indicating involvement of MAPK signalling pathway. Gene expression analysis of p53-dependent genes and bcl-2 gene family members confirmed differences between long and short-term rHuEpo effects, indicating the most prominent changes in BCL2 and BAD expression.

Conclusions: Proliferation and survival characteristics of MCF-7 cells are reversely modulated by the length of the rHuEpo exposure. On the other hand, MDA-MB-231 cells are almost irresponsive to long-term rHuEpo, supposedly due to the mutated p53 and ER(+)/PR(-) status. The p53 and ER/PR status may predict tumour response on rHuEpo and cDDP treatment.

No MeSH data available.


Related in: MedlinePlus