Abstract
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.
Highlights
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
We examined the potential functions of the Olfm[4] gene in murine prostate tissues by analyzing an Olfm4-knockout mouse model, and found that loss of Olfm[4] leads to neoplastic progression in the mouse prostate, as well as tumor formation in the lung, liver, and pancreas
Prostatic epithelial hyperplasia was seen at 3–6 months of age, prostatic intraepithelial neoplasia was observed at 10–12 months of age, and higher-grade prostate intraepithelial neoplasia was observed at 18–24 months of age in Olfm4-knockout mice (Supplementary Table S1)
Summary
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. We found that restoration of OLFM4 in human prostate-cancer cells that lack OLFM4 expression significantly downregulated hedgehog signaling-pathway component expression. Gene-expression data have revealed downregulation of the OLFM4 gene in prostate cancer, colon cancer, and leukemia, whereas OLFM4 expression was found to be upregulated in gastric cancer and pancreatic cancer These divergent results may be due to tissue- and cell-specific factors, as well as inflammation status and tumor grade[18]. We examined the potential functions of the Olfm[4] gene in murine prostate tissues by analyzing an Olfm4-knockout mouse model, and found that loss of Olfm[4] leads to neoplastic progression in the mouse prostate, as well as tumor formation in the lung, liver, and pancreas. We further explored the possible molecular mechanisms underlying prostate neoplastic progression in Olfm4-knockout mice and found that Olfm[4] negatively regulates the hedgehog-signaling pathway in mouse prostate. Our findings suggest that loss of olfactomedin 4 upregulates the hedgehog-signaling pathway and promotes progression of prostatic neoplasms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
