Suppression of breast cancer cell growth by her2-reduced AR serine 81 phosphorylation

Pao Hsuan Huang, Hsin Yi Wang, Chen Chuan Huang, Yueh Tsung Lee, Chia Herng Yue, Mei Chih Chen, Ho Lin

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Breast cancer is a hormone-related carcinoma and the most commonly diagnosed malignancy in women. Although Her-2, estrogen receptor (ER), and progesterone receptor (PR) are the major diagnostic markers and therapeutic targets to breast cancer, searching for additional molecular targets remains an important issue and one of the candidates is androgen receptor (AR). AR has been shown expressed in 70% breast cancer patients and connects to low recurrence and high survival rate. Our previous study demonstrates that Ser81 phosphorylation of AR in prostate cancer cells is critical for its protein stability modulated by human epidermal growth factor receptor-2 (Her2). The aim of this study is to investigate the influence of Her2 and AR in prolifer-ation of breast cancer cell line, MDA-MB-453. The data show that AR which was activated by synthetic androgen R1881 suppressed the proliferation of MDAMB-453 cells. Notably, AR activation decreased the protein levels of cell growth-related proteins, including cyclin A, cyclin B, and early growth response protein 1 (Egr1), while cell-cycle inhibitor protein p27 was increased. Besides, Heregulin (HRG)-induced Her2 activation decreased the AR protein levels and its Ser81 phosphorylation. Her2 small molecular inhibitor, Lapatinib, dose-dependently suppressed cell proliferation while the levels of phospho-Ser81 AR and p27 protein were increased. Phospho-Ser81 AR was also increased after Her2 knockdown. Specifically, the influence of phospho-Ser81 AR by Lapatinib was primarily found in the nucleus of MDA-MD-453 cells, where the cell proliferation might directly be interfered. In conclusion, our findings indicate that Her2 might negatively regulate AR phosphorylation/activation and contribute to regulate the proliferation of MDA-MB 453 cells.

Original languageEnglish (US)
Pages (from-to)232-239
Number of pages8
JournalChinese Journal of Physiology
Volume59
Issue number4
DOIs
StatePublished - 2016

    Fingerprint

Keywords

  • Androgen receptor
  • Breast cancer
  • Her2
  • Lapatinib
  • MDA-MB-453 cell line

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Huang, P. H., Wang, H. Y., Huang, C. C., Lee, Y. T., Yue, C. H., Chen, M. C., & Lin, H. (2016). Suppression of breast cancer cell growth by her2-reduced AR serine 81 phosphorylation. Chinese Journal of Physiology, 59(4), 232-239. https://doi.org/10.4077/CJP.2016.BAE416