Molecular mechanisms underlying progesterone-induced cytoplasmic retention of p27 in breast cancer cells

Hui Chen Wang, Wen Sen Lee

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


It has been reported that progesterone (P4) can contribute to the aggressiveness of human breast cancers through promoting cytoplasmic localization of p27 and stimulating proliferation. However, the molecular mechanisms underlying P4-induced cytoplasmic retention of p27 are still unclear. Here, we demonstrated that P4 (12.5–100 nM) concentration-dependently increased the number of T47D and MCF-7 cells. P4 (50 nM) also time-dependently increased the levels of p27 protein. Knock-down of p27 using the small interfering RNA (siRNA) technique abolished the P4-increased cell number of T47D and MCF-7. The signaling pathway involved in the P4-promoted breast cancer cell proliferation was further investigated. Our results suggest that P4 activated the PI3K/AKT-mediated signaling, subsequently increasing phophorylation of p27 at pT198 and T157, and thereby caused cytoplasmic retention of p27 protein. In addition, P4 activated kinase-interacting stathmin (KIS), subsequently increasing phosphorylation of nuclear p27 at serine 10 (S10), and thereby caused cytoplasmic translocation of p27pS10 from the nucleus. P4 also increased the level of nuclear CDK2pT160, thereby inducing p27 phosphorylation at T187, and hence caused cytosolic translocation of p27pT187 from the nucleus. In the cytosol, both p27pS10 and p27pT187 were degraded via the ubiquitin-proteasome pathway. Taken together, our data suggest that P4 promoted breast cancer cell proliferation through cytoplasmic retention of p27pT157 and p27pT198 and nuclear export of p27pS10 and p27pT187.

Original languageEnglish
Pages (from-to)202-209
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Publication statusPublished - Oct 2018


  • Kinase-interacting stathmin
  • p27pS10
  • p27pT157
  • p27pT187
  • p27pT198

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


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