Mutant p53 Gain of Function Contributes to Cancer Progression and Resistance to Therapy

Strategic Insights -

Research conducted by W.S. Yan and colleagues at the University of California has discovered a novel mechanism by which mutant p53 acquires its gain of function in cancer cells. The study found that mutant p53 can transactivate the GRO1 gene, leading to increased expression and contributing to cancer progression, invasion, and metastasis. This research has significant implications for the development of cancer therapies, suggesting that targeting GRO1 could be an effective treatment approach for a large portion of human tumors with mutant p53.

Key Takeaways:

  • Mutant p53 gain of function contributes to cancer progression, increased invasion and metastasis potentials, and resistance to anticancer therapy.
  • The ability of mutant p53 to acquire its gain of function is shown to correlate with increased expression of progrowth genes, such as c-MYC, MDR1, and NF-kappa B2.
  • Knockdown of mutant p53 inhibits GRO1 expression, while ectopic expression of mutant R175H in p53-null HCT116 cells increases GRO1 expression.
  • Endogenous mutant p53 is capable of binding to and activating the GRO1 promoter.
  • Ectopic expression of GRO1 can rescue the proliferative defect in SW480 and MIA-PaCa-2 cells induced by knockdown of mutant p53.
  • Knockdown of endogenous GRO1 inhibits cell proliferation and abrogates mutant p53 gain of function in SW480 cells.
  • Targeting GRO1 for cancer therapy may be applicable to a large portion of human tumors with mutant p53, but the mutation status of p53 should be taken into consideration.

Statistics:

  • 12178-12187: The page numbers where the research findings were published in the Journal of Biological Chemistry.
  • 2009: The year the research article was published.
  • 284: The volume number of the Journal of Biological Chemistry where the research article was published.
  • 18: The issue number of the Journal of Biological Chemistry where the research article was published.
  • 9650: The zip code of the American Society Biochemistry Molecular Biology Inc. in Bethesda, MD.
  • 3996: The suite number of the American Society Biochemistry Molecular Biology Inc. in Bethesda, MD.

Sources:

  • Yan, W.S., et al. Identification of GRO1 as a Critical Determinant for Mutant p53 Gain of Function. Journal of Biological Chemistry, 2009;284(18):12178-12187.
  • American Society Biochemistry Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA.
  • X.B. Chen, University of California, Center Comparative Oncology, 2128 Tupper Hall, Davis, CA 95616, USA.