Molecular Mechanism of Estrogen's Pro-Life Effect on Breast Cancer Cells Revealed

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Scientists at The University of Texas M. D. Anderson Cancer Center have made a breakthrough in understanding how the estrogen hormone helps keep breast cancer cells alive. The researchers have identified a complex molecular pathway involving multiple genes and proteins, including breast cancer-associated protein 3 (BCA3) and SIRT1, which is a key protein involved in this pathway. The study, published in Nature Cell Biology, assigns roles to these proteins and others, providing insights into potential molecular drug targets for breast cancer treatment.

Key Takeaways:

  • The researchers have identified a complex molecular pathway involving estrogen, BCA3, NEDD8, SENP8, SIRT1, and NFkB that contributes to breast cancer cell survival.
  • BCA3, a protein previously found to be over-expressed in both breast and prostate cancers, has been shown to have a role in this pathway as a tumor suppressor when modified by NEDD8.
  • SIRT1, a protein responsible for prolonging life span in both yeast and worms, has been found to be involved in suppressing cancer development by acting as a histone deacetylase.
  • The researchers have discovered that estrogen blocks NEDD8 from modifying BCA3, which goes some way to explaining estrogen's pro-life effect in breast cancer cells.
  • The study suggests that NEDD8 is a key player in this molecular pathway, and blocking its removal from BCA3 could be a potential therapeutic strategy for breast cancer treatment.
  • The researchers have identified potential molecular drug targets in this pathway, including NEDD8, SENP8, and SIRT1.

Statistics:

  • 70% of breast cancers are fueled by estrogen.
  • The researchers used yeast as their experimental platform to study this molecular pathway.
  • The study involved a four-member research team.
  • The recruited SNEP8, an enzyme that can break bonds between other molecules, as a tool to identify proteins that can be altered by NEDD8.
  • NEDD8-modified BCA3 binds to p65, one of the two proteins that make up NFkB, and regulates its activity.
  • When NEDD8-modified BCA3 binds to p65, it recruits SIRT1 to suppress NFkB-mediated transcription.

Sources:

  • Nature Cell Biology
  • The University of Texas M. D. Anderson Cancer Center