Gene profiling uncovers retinoid target genes.
Decades of hypothesis-driven research have identified candidate targets for cancer therapy and chemoprevention. Recently, genomic, proteomic, and tissue-based microarray approaches have made possible another scientific approach. This is one that interrogates comprehensively the complex profile of mRNA or protein expression present in normal, preneoplastic, or malignant cells and tissues. This in turn can uncover critical targets for cancer pharmacology and also lead to a better understanding of the known or novel networks of gene expression that play a rate-limiting role in carcinogenesis. This chapter addresses the use of mRNA expression profiling to uncover candidate target genes active in cancer pharmacology by citing as an example how this has already proven useful to reveal that retinoids (natural and synthetic derivatives of vitamin A) signal through pathways, which promote tumor cell differentiation, induce growth suppression, trigger apoptosis or affect other growth regulatory pathways. Pathways involved in the regulation of protein stability will be highlighted as these play a critical role in mediating pharmacological effects of the retinoids in cancer therapy or chemoprevention.
Ma
Yan
Y
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH, USA.
Feng
Qing
Q
Pitha-Rowe
Ian
I
Kitareewan
Sutisak
S
Dmitrovsky
Ethan
E
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002454:Cell Differentiation; D018890:Chemoprevention; D016503:Drug Delivery Systems; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012176:Retinoids / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D014407:Tumor Cells, Cultured
C119724:AGFG1 protein, human; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D012176:Retinoids; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human