The murine olfactomedin 4 gene (Olfm4) encodes an olfactomedin-related glycoprotein whose physiological and pathological functions in the prostate are largely unknown. We have observed that homozygous Olfm4 mutant mice develop prostatic intra epithelial neoplisa (PIN), high grade PIN, adenocarcinoma and metastatic tumor in an age-dependent manner. We also found that increased proliferation of prostate epithelial cells in Olfm4-null mice. In this report, we studied the mechanisms underlying neoplastic progression of Olfm4-deficient mice prostate. We have performed microarray analysis to compare Olfm4 knockout and wild-type mice prostate at 3 and 15 months of ages. A total of 187 genes were found commonly changed in both 3 and 15 months, whereas 894 and 1090 genes were significantly changed in 3 and 15 months respectively. Enrichment Gene Go Diseases analysis showed prostatic neoplasms was at the top of 10 listed diseases. We found that 95 genes for neoplastic procession markers were significantly changed in the prostate of Olfm4-deficient mice. Among the genes, 39 genes were up-regulated and 37 genes were down regulated more than 1.5-fold. The qRT-PCR confirmed consistently higher expression of Ets1, Vav3, Shh, Sdc2, and Mmp19, and down-regulation of the genes Rnasel and Psca in Olfm4 knockout mice compared with Olfm4 wild-type mice. We also confirmed expression of Ets1 and Mmp19 by using western blot and immunohistochemistry analysis.

Interestingly, in the GEO prostate cancer database, which compares tumor to normal tissue and metastatic tumor to normal tissue, expression of OLFM4 and RNASEL were down-regulated, in contrast, expression of ETS1 and MMP19 were up-regulated. Therefore, the gene expression profiles in the GEO database confirmed and extended Ets1, Mmp19 and Rnasel in Olfm4 knockout mice. Our finding indicates that loss of OLFM4 leads to progression of prostate cancer.

Citation Format: Hongzhen Li, Wenli Liu, Jianqiong Zhu, Weiping Chen, Chu-Xia Deng, Griffin P. Rodgers. Loss of Olfactomedin 4 gene leads to neoplastic progression in the murine prostate. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1990. doi:10.1158/1538-7445.AM2013-1990