Autocrine/paracrine mechanism of interleukin-17B receptor promotes breast tumorigenesis through NF-κB-mediated antiapoptotic pathway
Journal
Oncogene
Journal Volume
33
Journal Issue
23
Pages
2968-2977
Date Issued
2014
Author(s)
Huang C.-K.
Yang C.-Y.
Chen C.-L.
Wu H.-H.
Ma C.
Shew J.-Y.
Lee W.-H.
Abstract
Gain of function of membrane receptor was a good strategy exploited by cancer cells to benefit own growth and survival. Overexpression of HER2 has been found to serve as a target for developing trastuzumab to treat 20-25% of breast cancer. However, little or none of the other membrane receptor was found to be useful as a potential target for breast cancer treatment since then. Here, we showed that amplified signaling of interleukin-17 receptor B (IL-17RB) and its ligand IL-17B promoted tumorigenicity in breast cancer cells and impeded acinus formation in immortalized normal mammary epithelial cells. External signal transmitted through IL-17RB activated nuclear factor-κB to upregulate antiapoptotic factor Bcl-2 and induced etoposide resistance. Elevated expression of IL-17RB had a stronger correlation with poor prognosis than HER2 in breast cancer patients. Interestingly, breast cancer patients with high expression of IL-17RB and HER2 had the shortest survival rate. Depletion of IL-17RB in trastuzumab-resistant breast cancer cells significantly reduced their tumorigenic activity, suggesting that IL-17RB and HER2 have an independent role in breast carcinogenesis. Furthermore, treatment with antibodies specifically against IL-17RB or IL-17B effectively attenuated tumorigenicity of breast cancer cells. These results suggest that the amplified IL-17RB/IL-17B signaling pathways may serve as a therapeutic target for developing treatment to manage IL-17RB-Associated breast cancer.. ? 2014 Macmillan Publishers Limited All rights reserved 0950-9232/14.
SDGs
Other Subjects
caspase 3; epidermal growth factor receptor; epidermal growth factor receptor 2; etoposide; immunoglobulin enhancer binding protein; interleukin 17 receptor; interleukin 17b receptor; protein bcl 2; survivin; trastuzumab; tumor necrosis factor receptor associated factor 6; unclassified drug; X linked inhibitor of apoptosis; acinar cell; anchorage independent growth; apoptosis; article; breast cancer; breast carcinogenesis; breast epithelium; cancer cell; cancer growth; cancer prognosis; cancer resistance; cancer size; cancer survival; carcinogenic activity; controlled study; enzyme activation; gene amplification; human; human cell; priority journal; protein depletion; protein expression; signal transduction; upregulation; Animals; Apoptosis; Autocrine Communication; Breast Neoplasms; Carcinogenesis; Cell Line, Tumor; Etoposide; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-17; Mammary Neoplasms, Experimental; MCF-7 Cells; Mice; Mice, Inbred NOD; Mice, SCID; NF-kappa B; Paracrine Communication; Receptor, erbB-2; Receptors, Interleukin-17; Signal Transduction; Xenograft Model Antitumor Assays
Publisher
Nature Publishing Group
Type
journal article