ErbB receptor tyrosine kinase/NF-?B signaling controls mammosphere formation in human breast cancer.

ABSTRACT: 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-?B and by expression of I?B?-Super Repressor (I?B?SR), a dominant-negative inhibitor for NF-?B. Moreover, the overexpression of I?B?SR 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-?B pathway. These findings illustrate that HRG/ErbB3 signaling appears to maintain mammosphere formation through a PI3K/NF-?B pathway in human breast cancer.

SUBMITTER: Hinohara K 

PROVIDER: S-EPMC3340023 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature