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学科主题: 基础医学
题名:
A Role for the Clock Gene Per1 in Prostate Cancer
作者: Cao, Qi1,2; Gery, Sigal1; Dashti, Azadeh1; Yin, Dong1; Zhou, Yan2; Gu, Jiang2,3; Koeffler, H. Phiflip1
刊名: CANCER RESEARCH
发表日期: 2009-10-01
DOI: 10.1158/0008-5472.CAN-08-4199
卷: 69, 期:19, 页:7619-7625
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: NIGHT-SHIFT WORK ; MAMMALIAN CIRCADIAN CLOCK ; TUMOR-SUPPRESSOR ; BREAST-CANCER ; IN-VIVO ; EXPRESSION ; RISK ; TRANSCRIPTION ; CELLS ; OSCILLATORS
英文摘要:

Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbations of these rhythms are associated with pathogenic conditions, such as depression, diabetes, and cancer. Androgens play an important role in both normal development and carcinogenesis of the prostate. In the present study, we investigated a potential role for the core clock factor Per1 in the pathogenesis of prostate cancer. Serum-shocked synchronized prostate cancer cells displayed disrupted circadian rhythms compared with the normal prostate tissue. Using Oncomine to perform a meta-analysis of microarray expression studies, we found that Per1 is down-regulated in human prostate cancer samples compared with normal prostates. Reporter assays showed that Per1 inhibited transactivation of the androgen receptor (AR) both in 293T cells overexpressing the AR and in the prostate cancer cell line LNCaP. Forced expression of Per1 in LNCaP cells diminished the expression of known androgen-sensitive genes following stimulation with dihydrotestosterone. We showed that Per1 physically interacted with AR; in addition, we found that Per1 itself is regulated by androgens in prostate cancer cells. Overexpression of Per1 in prostate cancer cells resulted in significant growth inhibition and apoptosis. Our results support the emerging role of circadian genes as key players in malignant transformation. Further elucidating the connections between clock genes and the AR pathway could benefit the development of new therapeutic strategies for prostate cancer as well as provide insights into chronotherapy as away to optimize current therapies. [Cancer Res 2009;69(19):7619-25]

语种: 英语
项目资助者: NIH ; C. Koeffler finds, Inger Foundation ; China Scholarship Council
WOS记录号: WOS:000270487600019
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57398
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Shantou Univ, Coll Med, Shantou, Peoples R China
2.Univ Calif Los Angeles, Cedars Sinai Med Ctr, Div Hematol Oncol, Sch Med, Los Angeles, CA 90048 USA
3.Peking Univ, Dept Pathol, Sch Basic Med Sci, Beijing 100871, Peoples R China

Recommended Citation:
Cao, Qi,Gery, Sigal,Dashti, Azadeh,et al. A Role for the Clock Gene Per1 in Prostate Cancer[J]. CANCER RESEARCH,2009,69(19):7619-7625.
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