Role of interleukin-8 in the progression of estrogen receptor-negative breast cancer

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Background Estrogen receptor(ER)is a very important biomarker of breast cancer.ER deletion has been consistentlyassociated with tumor progression,recurrence,metastasis and poor prognosis,but the biological mechanism is stillunclear.ER negative breast cancer expresses high levels of interleukin-8(IL-8).ER expression can downregulate IL-8promotor activity.As a multifunctional cytokine,IL-8 has many important biological activities in tumor genesis anddevelopment.With the goal of investigating the role of IL-8 in ER-negative breast cancer progression,we applied RNAinterference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell lineMDA-MB-231.Methods Interfering pRNA-IL-8 and the control was transfected into ER(-)MDA-MB-231.The proliferation,cell apotosis,and invasive ability were recorded in transfected,untransfected and negative transfected cells.These cells were injectedinto nude mice to assess tumorigenicity,proliferation,metastasis and microvessel density(MVD).Results In vitro,decreased expression of IL-8 was associated with reduced cell invasion(P<0.001),but had no effecton cell proliferation(P>0.05).In vivo,neutrophils infiltration was significantly inhibited in pRNA-IL-8 transfected cellscompared with untransfected and negatively transfected cells(P=0.001,P<0.001).Less metastasis was found intransfected cells compared with negatively transfected cells(0% vs 80%,P=0.048).Nevertheless,we observed lessMVD in transfected cells compared with control in nude mice(P<0.001).Conclusions IL-8 inhibits ER-negative breast cancer cell growth and promotes its metastasis in vivo,which may becorrelated with neutrophils infiltration induced by IL-8. Background Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological mechanism is stillunclear. ER negative breast cancer expresses high levels of interleukin-8 ( IL-8 has many important biological activities in tumor genesis and development. What the goal of investigating the role of IL-8 in ER-negative breast cancer progression , we applied RNA interference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell line MDA-MB-231. Methods Interfering pRNA-IL-8 and the control was transfected into ER (-) MDA- proliferation, cell apotosis, and invasive ability were recorded in transfected, untransfected and negative transfected cells. The cells were injected in nude mice to assess tumorigenicity, proliferation, metastasis and microvesse Results of In vitro, decreased expression of IL-8 was associated with reduced cell invasion (P <0.001), but had no effect of cell proliferation (P> 0.05). In vivo, neutrophils infiltration was significantly inhibited in pRNA (P = 0.001, P <0.001) .Less metastasis was found in intransfected cells compared with negatively transfected cells (0% vs 80%, P = 0.048) in transfected cells compared with control in nude mice (P <0.001) .Conclusions IL-8 inhibits ER-negative breast cancer cell growth and promotes its metastasis in vivo, which may becorrelated with neutrophils infiltration induced by IL-8.
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