The interaction between androgen receptor and semenogelin I: a synthetic LxxLL peptide antagonist inhibits the growth of prostate cancer cells
| Autor: | Hiroki Ide, Hiroshi Miyamoto, Eiji Kashiwagi, Peng Li, Taichi Mizushima, Satoshi Inoue, Jinbo Chen, Bin Han, Koji Izumi |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cancer Research medicine.medical_specialty Transcription Genetic Seminal Vesicle Secretory Proteins 03 medical and health sciences Prostate cancer 0302 clinical medicine Chlorides Cell Movement Leucine Cell Line Tumor androgen receptor Internal medicine Coactivator LNCaP medicine Humans Molecular Diagnostics Cell Proliferation Alanine Chemistry Cell growth zinc semenogelin Prostatic Neoplasms Dihydrotestosterone Transfection LxxLL motif prostate cancer medicine.disease coactivator peptide Cell biology Androgen receptor 030104 developmental biology Endocrinology Semenogelin I Oncology Receptors Androgen Zinc Compounds 030220 oncology & carcinogenesis Mutation Peptides Sequence motif |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2017.404 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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