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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

(A and B) Venn’ diagrams representing differential gene expression at different rHuEpo treatments when compared to non-treated cells: (A) MCF-7; (B) MDA-MB-231 cell line. (C and D) Venn’ diagrams representing differential gene expression in cells that were or were not exposed to cDDP at different rHuEpo treatments: (C) MCF-7; (D) MDA-MB-231 cell line. ↑: up-regulation. ↓: down-regulation. Underlined = genes with non-matching direction of change.
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f5-rado-46-03-213: (A and B) Venn’ diagrams representing differential gene expression at different rHuEpo treatments when compared to non-treated cells: (A) MCF-7; (B) MDA-MB-231 cell line. (C and D) Venn’ diagrams representing differential gene expression in cells that were or were not exposed to cDDP at different rHuEpo treatments: (C) MCF-7; (D) MDA-MB-231 cell line. ↑: up-regulation. ↓: down-regulation. Underlined = genes with non-matching direction of change.

Mentions: rHuEpo effect. Venn diagrams on Figures 5A and 5B show genes that were differentially expressed upon short and long-term rHuEpo treatments when compared to un-stimulated control cells. In the MCF-7 cell line (Figure 5A), FOS and BCL2L1 were up-regulated and JUN was down-regulated after rHuEpo treatment independently of the treatment duration. BCL2 and CASP9 were up-regulated after short-term rHuEpo treatment, while long-term treatment down-regulated BCL2 together with BAD and up-regulated PMAIP1 and NF-κβ. In MDA-MB-231 cell line (Figure 5B) several genes were down-regulated after short-term treatment, namely BAD, BAX, BBC3 and PMAIP1, while the expression of BCL2L1 was increased. After long-term treatment, only BAD was deregulated; in contrast to short-term treatment, its increased expression was observed.


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)

(A and B) Venn’ diagrams representing differential gene expression at different rHuEpo treatments when compared to non-treated cells: (A) MCF-7; (B) MDA-MB-231 cell line. (C and D) Venn’ diagrams representing differential gene expression in cells that were or were not exposed to cDDP at different rHuEpo treatments: (C) MCF-7; (D) MDA-MB-231 cell line. ↑: up-regulation. ↓: down-regulation. Underlined = genes with non-matching direction of change.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-rado-46-03-213: (A and B) Venn’ diagrams representing differential gene expression at different rHuEpo treatments when compared to non-treated cells: (A) MCF-7; (B) MDA-MB-231 cell line. (C and D) Venn’ diagrams representing differential gene expression in cells that were or were not exposed to cDDP at different rHuEpo treatments: (C) MCF-7; (D) MDA-MB-231 cell line. ↑: up-regulation. ↓: down-regulation. Underlined = genes with non-matching direction of change.
Mentions: rHuEpo effect. Venn diagrams on Figures 5A and 5B show genes that were differentially expressed upon short and long-term rHuEpo treatments when compared to un-stimulated control cells. In the MCF-7 cell line (Figure 5A), FOS and BCL2L1 were up-regulated and JUN was down-regulated after rHuEpo treatment independently of the treatment duration. BCL2 and CASP9 were up-regulated after short-term rHuEpo treatment, while long-term treatment down-regulated BCL2 together with BAD and up-regulated PMAIP1 and NF-κβ. In MDA-MB-231 cell line (Figure 5B) several genes were down-regulated after short-term treatment, namely BAD, BAX, BBC3 and PMAIP1, while the expression of BCL2L1 was increased. After long-term treatment, only BAD was deregulated; in contrast to short-term treatment, its increased expression was observed.

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