BioProject

Loss of olfactomedin 4 (OLFM4) gene expression is associated with the progression of human prostate cancer, but its role and the molecular mechanisms involved in this process have not been completely understood. More...

Loss of olfactomedin 4 (OLFM4) gene expression is associated with the progression of human prostate cancer, but its role and the molecular mechanisms involved in this process have not been completely understood. In this study, we found that Olfm4-knockout mice developed prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Importantly, we found that the hedgehog-signaling pathway was significantly upregulated in the Olfm4-knockout mouse model. We also found that restoration of OLFM4 in human prostate-cancer cells that lack OLFM4 expression significantly downregulated hedgehog signaling-pathway component expression. Furthermore, we demonstrated that the OLFM4 protein interacts with sonic hedgehog protein, as well as significantly inhibits GLI-reporter activity. Bioinformatic and immunohistochemistry analyses revealed that decreased OLFM4 and increased SHH expression was significantly associated with advanced human prostate cancer. Thus, olfactomedin 4 appears to play a critical role in regulating progression of prostate cancer, and has potential as a new biomarker for prostate cancer. Overall design: Purpose: To explore the mechanisms underlying increased tumorigenesis of Olfm4-deficient murine prostate. Experiment design: Comparison of gene expression between Olfm4-knockout and wild-type mice at 3 months of age in the prostate tissue. Experimental procedures: Total RNA was purified from whole prostate tissue of Olfm4 (+/+) and Olfm4 (-/-) mice at 3 months of age using the RNeasy Plus Mini Kit (Qiagen). Microarray analyses were performed by the NIDDK Core Facility at the National Institutes of Health using Affymetrix Mouse Genome 430 2.0 Array GeneChips (Affymetrix; Santa Clara, CA). Biological replications were used for the Olfm4 (+/+) or Olfm4 (-/-) prostate RNA extracted from five individual mice. The microarray signals were analyzed using the Affymetrix RMA algorithm. The analysis of variance results, False Discovery Rate (FDR) reports, and heatmaps were generated using Partek Genomic of tware 6.5 (Partek; St. Charles, MO). Pathway analyses were performed using MetaCore webaccess software (http://www.genego.com/). Less...