Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells
- 5 June 2006
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 25 (55), 7311-7323
- https://doi.org/10.1038/sj.onc.1209715
Abstract
Progression of prostate cancer to androgen independence is suspected to involve the androgen and protein kinase A (PKA) signaling pathways. Here for the first time, the transcriptomes associated with each pathway and common transcriptional targets in response to stimulation of both pathways were identified in human prostate cancer cells using Affymetrix GeneChip technology (Human Genome U133 plus2). Statistically significant changes in the levels of 858 genes in response to androgen and 303 genes in response to activation of the PKA pathway were determined using GeneSpring software. Expression of a subset of these genes (22) that were transcriptional targets for the androgen and/or PKA pathways were validated by reverse transcriptase-polymerase chain reaction and Western blot analyses. Application of small interfering RNAs to the androgen receptor (AR) revealed that in addition to KLK3, levels of expression of KLK2 and SESN1 were regulated by AR activated by both the androgen and PKA signaling pathways. SESN1 was identified as a gene repressed by activated AR. These results provide a broad view of the effects of the androgen and PKA signaling pathways on the transcriptional program of prostate cancer cells and indicate that only a limited number of genes are targeted by cross-talk between AR and PKA pathways.This publication has 53 references indexed in Scilit:
- Amino-terminus domain of the androgen receptor as a molecular target to prevent the hormonal progression of prostate cancerJournal of Cellular Biochemistry, 2006
- Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell linesJournal of Pharmacy and Pharmacology, 2005
- Studies on Prostatic Cancer: I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the ProstateJournal of Urology, 2002
- p53 Represses Androgen-induced Transactivation of Prostate-specific Antigen by Disrupting hAR Amino- to Carboxyl-terminal InteractionJournal of Biological Chemistry, 2001
- Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1Genes & Development, 2001
- Significance analysis of microarrays applied to the ionizing radiation responseProceedings of the National Academy of Sciences of the United States of America, 2001
- CYCLIC AMP SIGNALING AND GENE REGULATIONAnnual Review of Nutrition, 1998
- Two Androgen Response Regions Cooperate in Steroid Hormone Regulated Activity of the Prostate-specific Antigen PromoterOnline Journal of Public Health Informatics, 1996
- Prostate-specific Antigen Expression Is Regulated by an Upstream EnhancerOnline Journal of Public Health Informatics, 1996
- Regulation of the mevalonate pathwayNature, 1990