Profiling of zinc-altered gene expression in human prostate normal vs. cancer cells: a time course study
| Autor: | Shu-fei Lin, Renty B. Franklin, Hua Wei, Pei Feng, Dennis L. Maeder |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Time Factors Endocrinology Diabetes and Metabolism Clinical Biochemistry Gene Expression chemistry.chemical_element Zinc Biology Biochemistry Article Cell Line Prostate cancer Prostate Cell Line Tumor Gene expression medicine Humans Metallothionein Molecular Biology Oligonucleotide Array Sequence Analysis Regulation of gene expression Genetics Nutrition and Dietetics Microarray analysis techniques Prostatic Neoplasms medicine.disease medicine.anatomical_structure chemistry Cancer cell Cancer research |
| Zdroj: | The Journal of Nutritional Biochemistry. 20:1000-1012 |
| ISSN: | 0955-2863 |
| DOI: | 10.1016/j.jnutbio.2008.09.004 |
| Popis: | We have demonstrated that zinc exposure induces apoptosis in human prostate cancer cells (PC-3) and benign hyperplasia cells (BPH), but not in normal prostate cells (HPR-1). However, the mechanisms underlying the effects of zinc on prostate cancer cell growth and zinc homeostasis remain unclear. To explore the zinc effect on gene expression profiles in normal (HPR-1) and malignant prostate cells (PC-3), we conducted a time course study of Zn treatment with microarray analysis. Microarray data were evaluated and profiled using computational approach for the primary and secondary data analyses. Final analyses were focused on the genes (1) highly sensitive to zinc; (2) associated with zinc homeostasis, i.e ., metallothioneins (MTs), solute zinc carriers (ZIPs) and zinc exporters (ZnTs); (3) relevant to several oncogenic pathways. Zinc-mediated mRNA levels of MT isotypes were further validated by semi-quantitative RT-PCR. Results showed that zinc effect on genome-wide expression patterns was cell-type specific, and zinc appeared to have mainly down-regulatory effects on thousands of genes (1953 in HPR-1; 3534 in PC-3) with a threshold of ±2.5-fold, while fewer genes were up-regulated (872 in HPR-1; 571 in PC-3). The patterns of zinc effect on functional MT genes' expression provided evidence for the cell type-dependent zinc accumulation and zinc-induced apoptosis in prostate cells. In PC-3 cells, zinc significantly up-regulated the expression of MT-1 isotypes MT-1J and MT-1M , denoted previously as "nonfunctional" MT genes, and now a depictive molecular structure of MT-1J was proposed. Examination of genes involved in oncogenic pathways indicated that certain genes, e.g. , Fos , Akt1 , Jak3 and PI3K , were highly regulated by zinc with cell-type specificity. This work provided an extensive database on zinc-related prostate cancer research. The strategy of data analysis was devoted to finding genes highly sensitive to Zn, and the genes associated with zinc accumulation and zinc-induced apoptosis. The results indicate that zinc regulation of gene expression is cell-type specific, and MT genes play important roles in prostate malignancy. |
| Databáze: | OpenAIRE |
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