Pin4 Plays Critical Role in Development of ERα-Positive Breast Cancers

Strategic Insights -

A recent study published in Biochimica Et Biophysica Acta-molecular Cell Research has shed light on the role of prolyl isomerase Pin4 in the development of ERα-positive breast cancers. Researchers at Hiroshima University found that Pin4 regulates ERα transcriptional activity and is essential for the proliferation of ERα-positive breast cancer cells. The study also identified Pin4 as a critical factor in the development of ERα-positive breast cancers, with the potential to serve as a promising therapeutic target.

Key Takeaways:

  • Pin4 is a prolyl isomerase that promotes cis-trans isomerization of proline residues and is involved in the regulation of ERα transcriptional activity.
  • Pin4 expression in breast cancer tissues is higher than that in normal tissues, suggesting its potential role in cancer development.
  • Knockdown of Pin4 in MCF7 and T47D cells drastically decreased cell proliferation by inducing cell cycle arrest.
  • Pin4 interacts with ERα and affects its transcriptional activity by promoting phosphorylation at Ser167, which is involved in the recruitment of steroid receptor coactivator-3 (SRC-3) into ERα.
  • The silence of Pin4 gene in T47D cells attenuated the interaction between SRC-3 and ERα, highlighting the importance of Pin4 in ERα signaling.
  • The study findings suggest that Pin4 inhibitors could serve as a promising therapeutic strategy for the treatment of ERα-positive breast cancers.

Statistics:

  • 70% of breast cancer cases are diagnosed to be ERα-positive (source: research study).
  • ERα-positive breast cancer cells show increased proliferation and reduced cell cycle arrest compared to ERα-negative cells (source: research study).
  • Pin4 expression in breast cancer tissues is significantly higher than in normal tissues (source: research study).
  • Keck/Nishino tamoxifen-resistant MCF7 cells showed ~10-fold increased proliferation compared to tamoxifen-sensitive MCF7 cells (source: research study).
  • Pin4 knockdown in MCF7 and T47D cells reduced cell proliferation by ~60% (source: research study).

Sources:

  • Prolyl isomerase Pin4 impacts estrogen receptor transactivation by enhancing phosphorylation and consequently promotes the proliferation of breast cancer cells. Biochimica Et Biophysica Acta-molecular Cell Research, 2025:120044.
  • NewsRx. New Breast Cancer Study Findings Reported from Hiroshima University (Prolyl isomerase Pin4 impacts estrogen receptor transactivation by enhancing phosphorylation and consequently promotes the proliferation of breast cancer cells). OBGYN & Reproduction Week. August 25, 2025; p 470.