Stable expression of C/EBPalpha in prostate cancer cells down-regulates metallothionein and increases zinc-induced toxicity.
BACKGROUND
The transcription factor C/EBPalpha regulates terminal differentiation of various cell types. C/EBPalpha 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/EBPalpha on the global gene expression profile in prostate cancer cells, we found that C/EBPalpha significantly decreased the RNA level of metallothioneins (MTs).


METHODS
The prostate cancer cell lines DU145, LNCaP, and PC3 with stable overexpression of C/EBPalpha 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/EBPalpha decreased expression of MT isoforms 1A, B, F, and H, IIA and III. Following zinc exposure C/EBPalpha inhibited MT promoter activity by 1.5-2.5-fold. Overexpression of C/EBPalpha led to increased cytotoxicity of zinc at concentration of 150 microM in DU145 and LNCaP cells.


CONCLUSIONS
Our data demonstrated that expression of MTs in prostate cancer cells is inhibited by C/EBPalpha and the effect may have functional significance in regulating the growth of prostate cancer cells and the response of these cells to environment stresses.
Yin
Hong
H
Feist-Weiller Cancer Center and Department of Medicine, Louisiana State University, Shreveport, Louisiana 71130, USA.
Smith
Mylinh
M
Glass
Jonathan
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D004273:DNA, Neoplasm; D008668:Metallothionein; D015032:Zinc