Profiling of zinc-altered gene expression in human prostate normal vs. cancer cells: a time course study.

摘要: Abstract We have demonstrated that zinc exposure induces apoptosis in human prostate cancer cells (PC-3) and benign hyperplasia (BPH), but not normal (HPR-1). However, the mechanisms underlying effects of on cell growth homeostasis remain unclear. To explore effect gene expression profiles (HPR-1) malignant (PC-3), we conducted a time course study Zn treatment with microarray analysis. Microarray data were evaluated profiled using computational approach for primary secondary analyses. Final analyses focused genes (1) highly sensitive to zinc; (2) associated homeostasis, i.e ., metallothioneins (MTs), solute carriers (ZIPs) exporters (ZnTs); (3) relevant several oncogenic pathways. Zinc-mediated mRNA levels MT isotypes further validated by semi-quantitative RT-PCR. Results showed genome-wide patterns was cell-type specific, appeared mainly down-regulatory thousands (1953 HPR-1; 3534 PC-3) threshold ±2.5-fold, while fewer up-regulated (872 571 PC-3). The functional genes' provided evidence type-dependent accumulation zinc-induced cells. In PC-3 cells, significantly MT-1 MT-1J MT-1M , denoted previously as "nonfunctional" genes, now depictive molecular structure proposed. Examination involved pathways indicated certain e.g. Fos Akt1 Jak3 PI3K regulated specificity. This work an extensive database zinc-related research. strategy analysis devoted finding Zn, apoptosis. results indicate regulation is play important roles malignancy.