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

Nina Trošt (Avtor), Peter Juvan (Avtor), Gregor Serša (Avtor), Nataša Debeljak (Avtor)

Povzetek

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 wer e cultured with or without rHuEpo for 24 h or 9 weeks and their growth characteristics after cDDP treatment were assessed together with expression ofgenes involved in the p53-signaling pathway. Results. Short-term exposure ofbreast 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.

Ključne besede

breast cancer;erythropoietin;cisplatin;cytotoxicity;

Podatki

Jezik:	Angleški jezik
Leto izida:	2012
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL MF - Medicinska fakulteta
Založnik:	Croatian Medical Association - Croatian Society of Radiology
UDK:	618.19-006.6-085
COBISS:	30028761
ISSN:	1318-2099
Matična publikacija:	Radiology and oncology
Št. ogledov:	29
Št. prenosov:	3
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarni naslov:	Nasproten vpliv rekombinantnega humanega eritropoetina na odgovor celic raka dojk na citotoksične učinke cisplatina
Sekundarne ključne besede:	rak dojk;eritropoetin;cisplatin;citotoksičnost;Breast neoplasms;Drug therapy;Cisplatin;Toxicity;Erythropoietin, recombinant;Cell division;Cell survival;Gene expression;Genes, p53;Genes, bcl-2;Tumor cells, cultured;
Vrsta dela (COBISS):	Delo ni kategorizirano
Komentar vira:	Soavtorji: Peter Juvan, Gregor Sersa, Natasa Debeljak; BSDOCID165025;
Strani:	str. 213-225
Letnik:	ǂVol. ǂ46
Zvezek:	ǂno. ǂ3
Čas izdaje:	2012
DOI:	10.2478/v10019-012-0037-8
ID:	23204824