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長庚大學 臨床醫學研究所

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特別演講 - 吳美誼 博士

Seminar
Synthetic Essentiality between Chromatin Remodeling Protein ARID4B and PTEN in Prostate Cancer
時間:108年 07月 04日 星期四 10:00 – 12:00
地點:長庚大學 第二醫學大樓會議廳B1 第二會議廳

abstract
PTEN is the most frequently mutated gene in human prostate cancer. Tumor suppressor function of PTEN is currently attributed to its lipid phosphatase activity that counters the PI3K action. Here, we report a novel PTEN-ARID4B-PI3K axis in which PTEN inhibits expression of ARID4B, while ARID4B serves as a transcriptional activator of the PI3K subunits PIK3CA and PIK3R2 crucial for activation of the PI3K/AKT pathway. Reciprocal binding of ARID4B and histone H1 to the PIK3CA and PIK3R2 promoters modulates chromatin condensation, suggesting a mechanism by which ARID4B activates these promoters. Functional analyses revealed that ARID4B is required for prostate tumorigenesis in the context of PTEN deficiency. The biological significance is substantiated by the PTEN/ARID4B/PIK3CA three-gene signature that improves the predictive power for prostate cancer recurrence in patients. Our findings identified ARID4B as a master regulator in the PTEN-PI3K pathway, thus providing a potential therapeutic target for prostate
cancer carrying PTEN mutations.
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