Targeting Tumor Oct4 to Deplete Prostate Tumor and Metastasis Initiating Cells
Technical Report,30 Sep 2015,29 Sep 2016
Southern Illinois University Springfield United States
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Identification of genes driving prostate carcinogenesis will lead to new cancer treatment. The human chromosome 8q24.21 region has been linked with increased risk for prostatic carcinoma but the how this region contributes to prostate carcinogenesis is unknown. We cloned a candidate gene, POU5F1B also called POU5F1P1, in this gene desert of 1.2Mb between FAM84B and the c-MYC oncogene. POU5F1B is a pseudogene of embryonic Oct4 POU5F1. A recent study found that tumor Oct4 found in prostate cancer cells is due to the gene expression of POU5F1B, not embryonic Oct4 POU5F1. In a dataset of 171 patients, it was found that tumor Oct4 was significantly increased in primary tumors and markedly increased in metastatic tumors, when compared to normal prostate or adjacent normal tissues. Based on the analyses and our preliminary data, we think, tumor Oct4, expressed from POU5F1B in the prostate cancer susceptibility loci 8q24, is a driver of prostate tumor formation and progression, and therefore, this driver is a novel target of intervention to eliminate prostate cancer. We propose to further determine the roles of tumor Oct4 in prostate tumor formation and metastasis. We hope we can validate whether tumor Oct4 can be targeted to inhibit prostate cancer progression and metastasis. In addition, we will map out the regions critical for Oct4 to promote prostate carcinogenesis so that we can target this region to develop therapeutics for cancer treatment in the future.
- Medicine and Medical Research