Targeted RASSF1A expression inhibits proliferation of HER2‑positive breast cancer cells in vitro

  • Authors:
    • Sai He
    • Yanni Hou
    • Leina Hou
    • Nan Chen
    • Xiaomin Yang
    • Huxia Wang
    • Pihua Han
    • Yongguo Fan
    • Jing Zhao
    • Jingyuan Zhang
    • Jie Geng
  • View Affiliations

  • Published online on: April 11, 2023     https://doi.org/10.3892/etm.2023.11944
  • Article Number: 245
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Abstract

Human epidermal growth factor receptor 2‑positive (HER2+) breast cancer, which accounts for 15‑20% of all breast cancer, is associated with tumor recurrence and poor prognosis. RAS association domain family protein 1 subtype A (RASSF1A) is a tumor suppressor that is silenced in a variety of human cancers. The present study aimed to investigate the role of RASSF1A in HER2+ breast cancer and the therapeutic potential of RASSF1A‑based targeted gene therapy for this malignancy. RASSF1A expression in human HER2+ breast cancer tissues and cell lines was evaluated by reverse transcription PCR and western blot analysis. The associations between tumorous RASSF1A level and tumor grade, TNM stage, tumor size, lymph node metastasis and five‑year survival were examined. HER2+ and HER2‑negative (HER2‑) breast cancer cells were transfected with a lentiviral vector (LV‑5HH‑RASSF1A) that could express RASSF1A under the control of five copies of the hypoxia‑responsive element (5HRE) and one copy of the HER2 promoter (HER2p). Cell proliferation was evaluated by the MTT and colony formation assays. It was found that tumorous RASSF1A level was negatively associated with tumor grade (P=0.014), TNM stage (P=0.0056), tumor size (P=0.014) and lymph node metastasis (P=0.029) and positively associated with five‑year survival (P=0.038) in HER2+ breast cancer patients. Lentiviral transfection of HER2+ breast cancer cells resulted in increased RASSF1A expression and decreased cell proliferation, especially under hypoxic conditions. However, lentiviral transfection of HER2‑breast cancer cells did not affect RASSF1A expression. In conclusion, these findings verified the clinical significance of RASSF1A as a tumor suppressor in HER2+ breast cancer and supported LV‑5HH‑RASSF1A as a potential targeted gene therapy for this malignancy.
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June-2023
Volume 25 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
He S, Hou Y, Hou L, Chen N, Yang X, Wang H, Han P, Fan Y, Zhao J, Zhang J, Zhang J, et al: Targeted RASSF1A expression inhibits proliferation of HER2‑positive breast cancer cells <em>in vitro</em>. Exp Ther Med 25: 245, 2023
APA
He, S., Hou, Y., Hou, L., Chen, N., Yang, X., Wang, H. ... Geng, J. (2023). Targeted RASSF1A expression inhibits proliferation of HER2‑positive breast cancer cells <em>in vitro</em>. Experimental and Therapeutic Medicine, 25, 245. https://doi.org/10.3892/etm.2023.11944
MLA
He, S., Hou, Y., Hou, L., Chen, N., Yang, X., Wang, H., Han, P., Fan, Y., Zhao, J., Zhang, J., Geng, J."Targeted RASSF1A expression inhibits proliferation of HER2‑positive breast cancer cells <em>in vitro</em>". Experimental and Therapeutic Medicine 25.6 (2023): 245.
Chicago
He, S., Hou, Y., Hou, L., Chen, N., Yang, X., Wang, H., Han, P., Fan, Y., Zhao, J., Zhang, J., Geng, J."Targeted RASSF1A expression inhibits proliferation of HER2‑positive breast cancer cells <em>in vitro</em>". Experimental and Therapeutic Medicine 25, no. 6 (2023): 245. https://doi.org/10.3892/etm.2023.11944