Activation of Thromboxane A(2) Receptors Induces Nurr1 Expression and Stimulates Cell Proliferation in Human Lung Cancer Cells

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A study published in Carcinogenesis details the activation of thromboxane A(2) receptors, which induces orphan nuclear receptor Nurr1 expression and stimulates cell proliferation in human lung cancer cells. Researchers at the University of Kentucky found that the activation of thromboxane A(2) receptor by its agonist I-BOP led to the expression of Nurr1, an orphan nuclear receptor implicated in cell proliferation, differentiation, and apoptosis. The study suggests that Nurr1 may mediate cyclin D1 expression and I-BOP-induced cell proliferation in human lung cancer cells.

Key Takeaways:

  • The activation of thromboxane A(2) receptors by its agonist I-BOP induces Nurr1 expression and stimulates cell proliferation in human lung cancer cells.
  • Nurr1, an orphan nuclear receptor, has been implicated in cell proliferation, differentiation, and apoptosis, and its expression is mediated through protein kinase A (PKA)/cAMP response element binding (CREB), protein kinase C, and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways.
  • The induction of Nurr1 expression by I-BOP is further investigated at the promoter level in H157 cells, revealing that Nurr1 expression is induced by I-BOP in a PKA/CREB-dependent manner.
  • Transcriptional activation of Nurr1 gene by I-BOP is further investigated using 5'-deletion analysis, site-directed mutagenesis, and luciferase reporter assay, demonstrating that Nurr1 expression is induced by I-BOP in a PKA/CREB-dependent manner.
  • Small interfering RNA of Nurr1 blocks I-BOP-induced cyclin D1 expression and cell proliferation and also decreases cell growth rate.
  • These results suggest that Nurr1 may mediate cyclin D1 expression and I-BOP-induced cell proliferation in human lung cancer cells.

Statistics:

  • 5'-Deletion analysis revealed that Nurr1 expression is induced by I-BOP in a PKA/CREB-dependent manner.
  • Site-directed mutagenesis and luciferase reporter assay demonstrated that Nurr1 expression is induced by I-BOP in a PKA/CREB-dependent manner.
  • 5'-Deletion analysis, site-directed mutagenesis, and luciferase reporter assay demonstrated that Nurr1 expression is induced by I-BOP in a PKA/CREB-dependent manner.
  • Nurr1 expression is induced by I-BOP in H157 cells in a PKA/CREB-dependent manner.

Sources:

  • Li, X., et al. (2009). Activation of thromboxane A(2) receptors induces orphan nuclear receptor Nurr1 expression and stimulates cell proliferation in human lung cancer cells. Carcinogenesis, 30(9), 1606-13.
  • University of Kentucky, Department of Pharmaceutical Sciences (2009). Gene Therapy Weekly editors from staff and other reports.