Abstract A47: Metastatic development of prostate cancer and multidrug resistance

Signaling pathway of androgen receptor plays a central role in the prostate cancer progression. Accordingly, approaches and molecular mechanisms to ablate the androgen receptor function in prostate cancer have been actively studied to improve the disease treatment. However, the disease inevitably develops resistance to all forms of hormonal therapies. To further understand metastatic prostate cancer, we established orthotopic xenograft model using various human cell lines expressing Luc2 reporter by lentivirus-mediated infection. Growth of these orthotopic xenografts develops a wide spectrum of spontaneous metastases in vivo, from which we also obtained cells from more aggressive and metastasized tumors. Indeed, cancer cells isolated from larger primary tumors and metastatic tumors are more invasive than those isolated from smaller primary tumors. Genome-wide RNA expression (transcriptomes) in cancer cells from metastases against primary large and small tumors were compared to reveal the difference between the different cancer stages. Real-time RT-PCR confirmation and Ingenuity Pathways Analysis (IPA) software analysis reveal activation of NFkB pathways and P-glycoprotein, so-called multidrug resistance-associated proteins in metastasis. Our study established useful cells and indicates a potential molecular basis of the drug resistance along the in vivo development of human prostate cancer. Supported by Academia Sinica, Career Development Award. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A47.