Cancer Institute A national cancer institute
designated cancer center
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Zijie Sun

Academic Appointments

  • Associate Professor of Urology

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Academic Appointments

Research & Scholarship

Current Research and Scholarly Interests

Transcriptional control is a key step in the regulation of eukaryotic gene expression. Our lab focuses on understanding the molecular mechanism of transcription factors that govern the transformation of normal mammalian cells to a neoplastic state. We are especially interested in the biological role of androgen receptor (AR), a nuclear hormone receptor, in development and related human diseases. Most prostate cancer cells express the AR and are androgen-dependent. Therefore, androgen ablation therapy has been routinely used for treatment of advanced prostate cancer. While the treatment initially achieves dramatic therapeutic response, it eventually fails in nearly all patients. Consequently, the patients develop castration resistant prostate cancer (CRPC) after two to three years following the therapy, for which there is no curable treatment. Our current efforts mainly focus on understanding the mechanisms underlying androgen signaling in prostate cancer progression and CRPC development. Ongoing projects in the lab are addressing several unknown and important questions in the field.

1) Multiple lines of evidence have shown a critical role of AR in ligand-independent prostate cancer cell growth, which implies that androgen-independent cells may still be “AR dependent” and that the AR can be used as a therapeutic target for future treatment. However, there is no appropriate animal model that can be used to directly evaluate ligand-independent AR action during the course of prostate cancer progression. We currently develop and generate a new generation of mouse models that can be used to recapitulate the critical role of AR during the course of disease progression. These mouse models are also important for future drug development.

2) Although nuclear hormone receptors in general are ligand-dependent transcriptional activators, their roles in transcriptional repression have also been suggested. We have identified a ligand induced AR repression on a pro-oncoprotein, c-Met, expression in prostate cancer cells. Because activation of c-Met induces prostate cancer invasion, metastasis, and hormonal refractoriness, our finding of the AR as a dual transcriptional activator and repressor in prostate cancer cells implies a novel molecular mechanism for prostate cancer progression and CRPC development. Our results further suggest that the current androgen ablation therapy may attenuate the repressive role of the AR on c-Met expression and actually induce CRPC development. Currently, we are using both in vitro and in vivo approaches to test our hypothesis in order to develop a more effective therapeutic strategy for patients.

3) AR-mediated transcription is facilitated through direct or indirect interactions with different signaling pathways and co-regulators. Emerging evidence suggests a promotional role of the Wnt/beta-catenin signaling pathway in prostate tumorigenesis. Because mutations in beta-catenin and other components of the beta-catenin destruction complex are rare in prostate cancer cells, the molecular mechanisms underlying beat-catenin oncogenic activation in prostate cancer may be different from those observed in human colorectal cancer or other malignancies. Currently, we are using several unique and novel models that were developed by us to investigate androgen and Wnt action and their interactions in prostate development and oncogenesis.




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