2. Academic Validation
  3. Autocrine/paracrine mechanism of interleukin-17B receptor promotes breast tumorigenesis through NF-κB-mediated antiapoptotic pathway

Autocrine/paracrine mechanism of interleukin-17B receptor promotes breast tumorigenesis through NF-κB-mediated antiapoptotic pathway

  • Oncogene. 2014 Jun 5;33(23):2968-77. doi: 10.1038/onc.2013.268.
C-K Huang 1,  C-Y Yang 2,  Y-M Jeng 3,  C-L Chen 2,  H-H Wu 2,  Y-C Chang 2,  C Ma 2,  W-H Kuo 4,  K-J Chang 5,  J-Y Shew 1,  W-H Lee 6
Affiliations

Affiliations

  • 1 1] Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan [2] Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • 2 Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • 3 Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
  • 4 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
  • 5 1] Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan [2] Cheng Chin General Hospital, Taichung, Taiwan.
  • 6 1] Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan [2] Genomics Research Center, Academia Sinica, Taipei, Taiwan [3] Department of Biological Chemistry, University of California, Irvine, CA, USA.
PMID: 23851503 DOI: 10.1038/onc.2013.268
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.

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