Fresh Data on Cancer Gene Therapy Reveals New Insights into Kidney Cancer Treatment

Strategic Insights -

Researchers in Strasbourg, France have made a significant discovery in the field of cancer gene therapy, shedding light on the role of the von Hippel-Lindau (VHL) tumor suppressor gene in renal cell carcinoma (RCC). According to a report published in Carcinogenesis, the researchers found that parathyroid hormone-related protein (PTHrP) is a survival factor for RCC, and its expression is negatively regulated by the VHL tumor suppressor gene at the level of messenger RNA (mRNA) stability. The study, led by S. Danilin and colleagues from the University of Louis Pasteur, aimed to analyze the alternative splicing of PTHrP mRNA in human RCC and identify VHL/hypoxia-induced factor (HIF) system-regulated mRNA-binding proteins involved in PTHrP mRNA stability.

Key Takeaways:

  • The VHL tumor suppressor gene plays a crucial role in regulating the expression of parathyroid hormone-related protein (PTHrP) in human renal cell carcinoma (RCC).
  • The PTHrP mRNA isoform 141 is predominantly expressed in RCC cells and tumors, and its expression is decreased by 50% in cells transfected with VHL.
  • Eight proteins with molecular weights ranging from 20 to 75 kDa bind to biotinylated transcripts spanning the 141 PTHrP mRNA AU-rich 3'-untranslated region, and their abundance is dependent on VHL expression.
  • The protein with an apparent molecular weight of 30 kDa was identified as HuR, a RNA-binding protein with stabilizing functions on various mRNA coding for proteins important in malignant transformation.
  • PTHrP expression studies confirmed the involvement of HuR in PTHrP upregulation in RCC.
  • The researchers concluded that common mRNA-binding proteins regulated by the VHL/HIF system may constitute new therapeutic opportunities against human RCC that remains refractory to therapies.

Statistics:

  • 80% of PTHrP mRNA isoform 141 was found in all cells and tumors.
  • 50% decrease in PTHrP mRNA expression was observed in cells transfected with VHL.
  • 30 kDa is the apparent molecular weight of the HuR protein.
  • 20-75 kDa is the range of molecular weights of the proteins binding to PTHrP mRNA.
  • VHL/HIF system-regulated mRNA-binding proteins may offer new therapeutic opportunities against RCC.

Sources:

  • Danilin S, et al. "Von Hippel-Lindau tumor suppressor gene-dependent mRNA stabilization of the survival factor parathyroid hormone-related protein in human renal cell carcinoma by the RNA-binding protein HuR." Carcinogenesis, 2009;30(3):387-96.
  • Cancer Gene Therapy Week editors. "Fresh Data on Cancer Gene Therapy Reveals New Insights into Kidney Cancer Treatment." Cancer Gene Therapy Week, 2009.