The three proteins reported in JCI are activated in a pathway involved in the aggressive form of the disease.

Three proteins, eNOS, ERß, and HIF-2a, can serve as biomarkers for aggressive prostate cancer, according to a research team from Regina Elena Cancer Institute, Italy. They report their findings in the Journal of Clinical Investigation in a paper titled “Endothelial NOS, estrogen receptor-beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer.”

The scientists were trying to define a molecular mechanism underlying the most aggressive form of prostate cancer. Using cultured cells taken from patients, they specifically looked at a pathway involving the activation of proteins eNOS, HIF-2a, and ERß.

Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERß/eNOS, ERß/HIF-1a, or ERß/HIF-2a combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes.

Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins. The scientists report that expression of eNOS plus ERß and nuclear eNOS plus HIF-2a were the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in prostate cancer progression.

Past Prostate Cancer Biomarker and Diagnostic Stories
New Gene Fusion Identified as Potential Prostate Cancer Biomarker (April 10, 2009)
Scientists Find Biomarker for Fatal Prostate Cancer (Feb. 13, 2009)
Group of Metabolites Linked to Aggressive Prostate Cancer (Feb. 12, 2009)
Health Discovery Enters Deals with Abbott and Quest Diagnostics for Prostate Cancer Tests (Feb. 6, 2009)
Clarient and Health Discovery to Offer Molecular-Based Test for Prostate Cancer (Jan. 13, 2009)


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