期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：17
页码：6584-6589
DOI：10.1073/pnas.1113271109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Breast cancer is one of the most common cancers in humans. However, our understanding of the cellular and molecular mechanisms underlying tumorigenesis in breast tissues is limited. Here, we identified a molecular mechanism that controls the ability of breast cancer cells to form multicellular spheroids (mammospheres). We found that heregulin (HRG), a ligand for ErbB3, induced mammosphere formation of a breast cancer stem cell (BCSC)-enriched population as well as in breast cancer cell lines. HRG-induced mammosphere formation was reduced by treatment with inhibitors for phosphatidyl inositol 3-kinase (PI3K) or NF-{kappa}B and by expression of I{kappa}B-Super Repressor (I{kappa}BSR), a dominant-negative inhibitor for NF-{kappa}B. Moreover, the overexpression of I{kappa}BSR in breast cancer cells inhibited tumorigenesis in NOD/SCID mice. Furthermore, we found that the expression of IL8, a regulator of self-renewal in BCSC-enriched populations, was induced by HRG through the activation of the PI3K/NF-{kappa}B pathway. These findings illustrate that HRG/ErbB3 signaling appears to maintain mammosphere formation through a PI3K/NF-{kappa}B pathway in human breast cancer.
关键词：EGF ; HER ; tumor sphere ; cancer stem cells ; inflammation
