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Oncogene ; 22(2): 256-65, 2003 Jan 16.
Article in English | MEDLINE | ID: mdl-12527894

ABSTRACT

Estrogen-receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that interleukin-8 (IL-8) was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ER-negative MDA-MB-231 cells, and we show that IL-8 produced by breast cancer cells is identical to monocyte-derived IL-8. Interestingly, the invasion potential of ER-negative breast cancer cells is associated at least in part with expression of IL-8, but not with IL-8 receptor levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by two fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ER-negative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness.


Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Interleukin-18/metabolism , Receptors, Estrogen/metabolism , Amino Acid Sequence , Base Sequence , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinogenicity Tests , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Cell Division/drug effects , Cell Division/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Interleukin-18/genetics , Interleukin-18/pharmacology , Molecular Sequence Data , Neoplasm Invasiveness , Tumor Cells, Cultured
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