Cullin1 is a novel marker of poor prognosis and a potential therapeutic target in human breast cancer

Ann Oncol. 2013 Aug;24(8):2016-22. doi: 10.1093/annonc/mdt147. Epub 2013 Apr 16.

Abstract

Background: To investigate the role of Cullin1 (Cul1) in the development of breast cancer, we examined the expression of Cul1 in breast cancer tissues and analyzed the correlation between Cul1 expression and clinicopathologic variables and patients survival.

Patients and methods: We evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) which includes 393 breast cancer tissues. We also studied the role of Cul1 in breast cancer cell proliferation, migration and invasion by carrying out CCK8 cell proliferation assay, cell migration and invasion assay.

Results: The Cul1 expression was significantly correlated with breast cancer histology grade (P = 0.000), estrogen receptor status (P = 0.001), progesterone receptor status (P = 0.001) and human epidermal growth factor receptor 2 status (P = 0.002). Furthermore, we showed a strong correlation between high Cul1 expression and worse 5-year overall and disease-specific survival rates in breast cancer patients (P = 0.026 and P = 0.015, respectively). Finally, we found that Cul1 knockdown inhibits cell proliferation, migration and invasion abilities.

Conclusions: Cul1 overexpression is significantly correlated with breast cancer progression and predicts worse survival. Cul1 regulates breast cancer cell proliferation, migration and invasion.

Keywords: breast cancer; cullin1; migration, invasion; prognostic; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cullin Proteins / biosynthesis
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism*
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival
  • Tissue Array Analysis
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

  • Biomarkers, Tumor
  • Cullin 1
  • Cullin Proteins
  • RNA, Small Interfering
  • Receptors, Estrogen
  • Receptors, Progesterone
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Matrix Metalloproteinase 2