Cell Adhesion Regulates Expression of the Androgen Receptor and Coregulators in Different Prostate Cancer Cells

International Journal of Molecular Sciences

Jie Zhang¹  Jia-Qing Xiang¹  Ya-Wei Zhang¹  Yan-Yan Chen¹  Xiao-Yan Zhou¹  Yun Liu² 

[1] Department of Thoracic Surgery, Shanghai Cancer Hospital, Fudan University, Shanghai 200032, P.R.China;Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, Shanghai 200031, P.R.China;

关键词: androgen receptor;    adhesion;    suspension;    prostate cancer;   

DOI  :  10.3390/i8020156

来源: mdpi

【 摘 要 】

Prostate cancer cells adhere to a tumor basement membrane, while secretory epithelial cells reside in a suprabasal cell compartment. Since tumor cells are derived from suprabasal epithelial cells, they experience de-novo substratum adhesion in the context of oncogenesis. We therefore analyzed whether cell-matrix adhesion could affect the protein expression and activity of the AR. In this study, AR protein expression declined upon suspension of BPH-1-AR cells, but not in PC-3-AR cells shown by Western blot. In a time course study, BPH-1 cell lost AR expression within 6 hours, and the synthetic androgen, R1881 reduced the loss of AR expression. We further explored the mechanism of AR loss in suspended BPH-1 cells. BPH-1-AR cells underwent apoptosis (anoikis) when suspended for 2 – 5 hours. Suspension did not induce significant apoptosis or decreasing of AR expression in PC-3 cells. Inhibition of apoptosis in suspended BPH-1-AR cells, either by expression of Bcl-2 or Bcl-xl or by treatment with Z-VAD, a caspase inhibitor, prevented loss of AR protein. In contrast, the calpain protease inhibitor, ALLN, accelerated the loss of AR protein expression. Additionally, cell-matrix adhesion changed the expression of coregulators of AR in the mRNA level of prostate cancer cells. Our results demonstrate that AR protein expression was reduced through activation of cell death pathways, and thus indirectly through cell suspension in BPH-AR cells. The activity of AR can also be regulated by adhesion in PC-3-AR and LNCaP cells through affecting the coregulators level.

【 授权许可】

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