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Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo

  • Authors:
    • Chen Yao
    • Kuan-Ping Yu
    • William Philbrick
    • Ben-Hua Sun
    • Christine Simpson
    • Changqing Zhang
    • Karl Insogna
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA, Department of Orthopaedics, Shanghai Jiaotong University Affiliated Shanghai No. 6 People's Hospital, Shanghai 200233, P.R. China
    Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1067-1077
    |
    Published online on: August 4, 2017
       https://doi.org/10.3892/ijmm.2017.3091
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Abstract

Breast cancer-associated gene 3 (BCA3) is a recently identified adaptor protein whose functions are still being defined. BCA3 has been reported to be an important regulator of nuclear factor-κB (NF-κB) signaling. It has also been reported to interact with the small GTPase, Rac1. Consistent with that observation, in the present study, BCA3 was found to interact with nuclear Rac1 in 293 cells and influence NF-κB signaling. Additional experiments revealed that depending on cell type, BCA3 augmented, attenuated or had no effect on NF-κB signaling in vitro. Since canonical NF-κB signaling is a critical downstream target from activated receptor activator of nuclear factor κB (RANK) that is required for mature osteoclast formation and function, BCA3 was selectively overexpressed in osteoclasts in vivo using the cathepsin K promoter and the response to exogenous receptor activator of nuclear factor κB ligand (RANKL) administration was examined. Despite its ability to augment NF-κB signaling in other cells, transgenic animals injected with high-dose RANKL had the same hypercalcemic response as their wild‑type littermates. Furthermore, the degree of bone loss induced by a 2-week infusion of low-dose RANKL was the same in both groups. Combined with earlier studies, the data from our study data indicate that BCA3 can affect NF-κB signaling and that BCA3 plays a cell-type dependent role in this process. The significance of the BCA3/NF-κB interaction in vivo in bone remains to be determined.
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Copy and paste a formatted citation
Spandidos Publications style
Yao C, Yu K, Philbrick W, Sun B, Simpson C, Zhang C and Insogna K: Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo. Int J Mol Med 40: 1067-1077, 2017.
APA
Yao, C., Yu, K., Philbrick, W., Sun, B., Simpson, C., Zhang, C., & Insogna, K. (2017). Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo. International Journal of Molecular Medicine, 40, 1067-1077. https://doi.org/10.3892/ijmm.2017.3091
MLA
Yao, C., Yu, K., Philbrick, W., Sun, B., Simpson, C., Zhang, C., Insogna, K."Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo". International Journal of Molecular Medicine 40.4 (2017): 1067-1077.
Chicago
Yao, C., Yu, K., Philbrick, W., Sun, B., Simpson, C., Zhang, C., Insogna, K."Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo". International Journal of Molecular Medicine 40, no. 4 (2017): 1067-1077. https://doi.org/10.3892/ijmm.2017.3091
Copy and paste a formatted citation
x
Spandidos Publications style
Yao C, Yu K, Philbrick W, Sun B, Simpson C, Zhang C and Insogna K: Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo. Int J Mol Med 40: 1067-1077, 2017.
APA
Yao, C., Yu, K., Philbrick, W., Sun, B., Simpson, C., Zhang, C., & Insogna, K. (2017). Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo. International Journal of Molecular Medicine, 40, 1067-1077. https://doi.org/10.3892/ijmm.2017.3091
MLA
Yao, C., Yu, K., Philbrick, W., Sun, B., Simpson, C., Zhang, C., Insogna, K."Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo". International Journal of Molecular Medicine 40.4 (2017): 1067-1077.
Chicago
Yao, C., Yu, K., Philbrick, W., Sun, B., Simpson, C., Zhang, C., Insogna, K."Breast cancer-associated gene 3 interacts with Rac1 and augments NF-κB signaling in vitro, but has no effect on RANKL-induced bone resorption in vivo". International Journal of Molecular Medicine 40, no. 4 (2017): 1067-1077. https://doi.org/10.3892/ijmm.2017.3091
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