Oncogene · 2023
The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Li Zhiping, Jiao Xuanmao, Robertson A Gordon, Di Sante Gabriele, Ashton Anthony W, DiRocco Agnese, Wang Min, Zhao Jun, Addya Sankar, Wang Chenguang, McCue Peter A, South Andrew P, Cordon-Cardo Carlos, Liu Runzhi, Patel Kishan, Hamid Rasha, Parmar Jorim, DuHadaway James B, Jones Steven J M, Casimiro Mathew C, Schultz Nikolaus, Kossenkov Andrew, Phoon Lai Yee, Chen Hao, Lan Li, Sun Yunguang, Iczkowski Kenneth A, Rui Hallgeir, Pestell Richard G
Аннотация
Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies.