染色质相关蛋白SIN3B通过诱导衰老来阻止前列腺癌进展。
Chromatin-Associated Protein SIN3B Prevents Prostate Cancer Progression by Inducing Senescence.
作者信息
Bainor Anthony J, Deng Fang-Ming, Wang Yu, Lee Peng, Cantor David J, Logan Susan K, David Gregory
机构信息
Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, New York.
Department of Pathology, NYU Langone Medical Center, New York, New York.
出版信息
Cancer Res. 2017 Oct 1;77(19):5339-5348. doi: 10.1158/0008-5472.CAN-16-3410. Epub 2017 Aug 14.
Abstract
Distinguishing between indolent and aggressive prostate adenocarcinoma remains a priority to accurately identify patients who need therapeutic intervention. SIN3B has been implicated in the initiation of senescence Here we show that in a mouse model of prostate cancer, SIN3B provides a barrier to malignant progression. SIN3B was required for PTEN-induced cellular senescence and prevented progression to invasive prostate adenocarcinoma. Furthermore, SIN3B was downregulated in human prostate adenocarcinoma correlating with upregulation of its target genes. Our results suggest a tumor suppressor function for SIN3B that limits prostate adenocarcinoma progression, with potential implications for the use of SIN3B and its target genes as candidate diagnostic markers to distinguish indolent from aggressive disease. .
摘要
区分惰性和侵袭性前列腺腺癌仍然是准确识别需要治疗干预患者的首要任务。SIN3B与衰老的起始有关。在此我们表明，在前列腺癌小鼠模型中，SIN3B为恶性进展提供了一道屏障。PTEN诱导的细胞衰老需要SIN3B，并可防止进展为侵袭性前列腺腺癌。此外，SIN3B在人类前列腺腺癌中下调，与其靶基因的上调相关。我们的结果表明SIN3B具有肿瘤抑制功能，可限制前列腺腺癌的进展，这对于将SIN3B及其靶基因用作区分惰性疾病和侵袭性疾病的候选诊断标志物具有潜在意义。
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