Upregulation of PSMD4 gene by hypoxia in prostate cancer cells

Turkish journal of biology

article

SÜMEYYE AYDOGAN TÜRKOĞLU¹  GİZEM DAYI²  FERAY KÖÇKAR¹ 

[1] Department of Molecular Biology and Genetics, Faculty of Science and Literature, University of Balıkesir;Department of Biology, Faculty of Science and Literature, University of Balıkesir

关键词: PSMD4;    hypoxia;    transcriptional regulation;    prostate cancer;    endothelial cells;   

DOI  :  10.3906/biy-2002-71

学科分类：生物科学（综合）

来源: Scientific and Technical Research Council of Turkey - TUBITAK

【 摘 要 】

Ubiquitin-proteasome pathways have a crucial role in tumor progression. PSMD4 (Rpn10, 26S proteasome non-ATPase subunit 4), which is a subunit of the regulatory particle, is a major ubiquitin (Ub) receptor of 26S proteasome. PSMD4 overexpression has been observed in colon carcinoma, hepatocellular carcinoma, and breast cancer. In this work, we elucidated the effect of hypoxia on PSMD4 gene expression in prostate cancer cells (PC3). Chemically mimicked hypoxia drastically upregulated PSMD4 gene expression at both mRNA and protein levels. Transient transfection experiments indicated that all promoter fragments were active in PC3 cells. Hypoxia increased transcriptional activity of all PSMD4 promoter constructs. EMSA analysis shows that HIF-1a transcription factor binds to the hypoxia response element (HRE) present within the -98/+52 region of PSMD4 promoter. We also used human umbilical vein endothelial cell (HUVEC) as a different cell model, in which increased PSMD4 expression was seen only at 24 h. The increased expression of the PSMD4 level in the PC3 cell line was not parallel to the expression in hypoxic HUVEC.

【 授权许可】

Unknown