Posttranscription regulation of prostate cancer growth.
Advances in the understanding of the molecular mechanisms implicated in prostate cancer progression have allowed identification of many potential therapeutic gene targets that are involved in apoptosis, growth factors, cell signaling, and the androgen receptor. A critical factor responsible for the malignant progression of prostate cancer is the abnormal expression and function of specific proteins. From the transcription of mRNA to the translation of proteins and their function, several steps can be exploited as "drugable" targets. In this article we will review some of the key molecular targets and posttranscriptional strategies that are currently being tested both preclinically and clinically as targeted therapeutic approach for prostate cancer. Most of the targets mentioned in this review involve the prostate cancer signal transduction cascade, and their functions include prosurvival, antiapoptosis, and proangiogenesis. We will focus in particular on the emerging role of the "chromatin modifiers," histone deacetylase inhibitors, not only in transcriptional gene regulation but also in posttranscriptional protein modifications as a tool for therapeutic intervention in prostate cancer.
Shen
Li
L
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Pili
Roberto
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D051152:Clusterin / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008297:Male; D063151:Polycomb Repressive Complex 2; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger; D014157:Transcription Factors / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000187:drug effects; D051020:bcl-X Protein / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D051152:Clusterin; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D051020:bcl-X Protein; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2