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Stable expression of C/EBPα in prostate cancer cells down‐regulates metallothionein and increases zinc‐induced toxicity
Author(s) -
Yin Hong,
Smith Mylinh,
Glass Jonathan
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20136
Subject(s) - metallothionein , prostate cancer , toxicity , zinc , prostate , cancer research , cancer , medicine , biology , chemistry , organic chemistry
BACKGROUND The transcription factor C/EBPα regulates terminal differentiation of various cell types. C/EBPα is expressed in prostate epithelium but its role in prostate development and malignant transformation is unknown. In examining the effect of forced expression of C/EBPα on the global gene expression profile in prostate cancer cells, we found that C/EBPα significantly decreased the RNA level of metallothioneins (MTs). METHODS The prostate cancer cell lines DU145, LNCaP, and PC3 with stable overexpression of C/EBPα were established with a retroviral expression system. MT expression was assayed by Western blot analysis and with the MT promoter in a plasmid using luciferase as a reporter. RESULTS Under basal conditions and in response to zinc, forced overexpression of C/EBPα decreased expression of MT isoforms 1A, B, F, and H, IIA and III. Following zinc exposure C/EBPα inhibited MT promoter activity by 1.5–2.5‐fold. Overexpression of C/EBPα led to increased cytotoxicity of zinc at concentration of 150 μM in DU145 and LNCaP cells. CONCLUSIONS Our data demonstrated that expression of MTs in prostate cancer cells is inhibited by C/EBPα and the effect may have functional significance in regulating the growth of prostate cancer cells and the response of these cells to environment stresses. © 2004 Wiley‐Liss, Inc.