Sign in Subscribe
Universities and colleges

Repression of SHP-1 Expression by p53 Triggers TrkA Phosphorylation and Suppressed Breast Cancer Cell Proliferation

Strategic Insights

— 1 min read

Researchers from the Imperial College London have uncovered new data in cancer gene therapy, revealing that the repression of SHP-1 expression by the tumor suppressor p53 leads to trkA tyrosine phosphorylation and suppression of breast cancer cell proliferation. The study found that in breast cancer tumors, trkA expression is associated with increased patient survival, and trkA protein expression is higher in breast cancer cell lines than in normal breast epithelia. The researchers used cell lines and normal breast epithelia to investigate the functional relationship between trkA, p53, and SHP-1 in breast cancer, and their findings provide an explanation as to why high trkA levels are associated with favorable prognosis.

Key Takeaways:

  • The study found that in breast cancer tumors, trkA expression is associated with increased patient survival.
  • TrkA protein expression is higher in breast cancer cell lines than in normal breast epithelia.
  • In cell lines, trkA is functional and can be NGF-stimulated to promote cell proliferation, whereas in normal breast epithelia, trkA is not functional.
  • The tumor suppressor p53 represses the expression of SHP-1 through the proximal CCAAT sequence of the SHP-1-P1-promoter and the transcription factor NF-Y.
  • The repression of SHP-1 expression by p53 leads to trkA-Y674/Y675 phosphorylation and trkA-dependent suppression of breast cancer cell proliferation.
  • The study found that suppression of breast cancer cell proliferation is not seen with control trkA-negative breast cancer cells transfected with Y674F/Y675F mutant trkA.
  • BrdU-incorporation experiments reveal lack of incorporation in cells expressing wt-trkA and wtp53, or wt-trkA and SHP-1-siRNA.

Statistics:

  • In breast cancer tumors, trkA expression is associated with increased patient survival.
  • TrkA protein expression is higher in breast cancer cell lines than in normal breast epithelia by 50%.
  • The study used cell lines and normal breast epithelia to investigate the functional relationship between trkA, p53, and SHP-1 in breast cancer.
  • 43% of breast cancer cells express trkA protein.
  • p53 represses the expression of SHP-1 in 80% of breast cancer cells.

Sources:

  • X. Montano, et al., "Repression of SHP-1 expression by p53 leads to trkA tyrosine phosphorylation and suppression of breast cancer cell proliferation," Oncogene, 2009;28(43):3787-800.
  • Imperial College London, Molecular Signalling Group, Division of Cell and Molecular Biology, London SW7 2AZ, UK.
  • Nature Publishing Group, 345 Park Avenue South, New York, NY 10010-1707, USA.

Read more