The interaction between androgen receptor and semenogelin I: A synthetic LxxLL peptide antagonist inhibits the growth of prostate cancer cells

Peng Li, Jinbo Chen, Eiji Kashiwagi, Taichi Mizushima, Bin Han, Satoshi Inoue, Hiroki Ide, Koji Izumi, Hiroshi Miyamoto

Research output: Contribution to journalArticlepeer-review

Abstract

Background:We previously demonstrated that a seminal plasma protein, semenogelin I (SgI), functioned as an androgen receptor (AR) coactivator. Meanwhile, several short sequence motifs in AR coregulators, such as LxxLL (L=leucine), have been shown to mediate specific interactions with AR.Methods:We investigated the role of the LxxLL motif within SgI in the interactions with AR and cell growth in prostate cancer lines in vitro.Results:A full-length SgI with mutations in the motif (i.e., LxxAA; A=alanine) failed to significantly increase cell proliferation/migration as well as androgen-mediated AR transcription. Co-immunoprecipitation showed no physical interactions between AR and the mutant SgI. In addition, transfection of an 18-amino acid peptide of SgI containing LxxLL, but not LxxAA, resulted in considerable reduction in cell growth and prostate-specific antigen expression in LNCaP and C4-2 lines.Conclusions:The LxxLL motif of SgI could be a novel therapeutic target for both androgen-sensitive and castration-resistant prostate cancers.

Original languageEnglish
Pages (from-to)416-420
Number of pages5
JournalBritish journal of cancer
Volume118
Issue number3
DOIs
Publication statusPublished - Feb 6 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The interaction between androgen receptor and semenogelin I: A synthetic LxxLL peptide antagonist inhibits the growth of prostate cancer cells'. Together they form a unique fingerprint.

Cite this