期刊
CANCER RESEARCH
卷 74, 期 4, 页码 1141-1152出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-13-2247
关键词
-
类别
资金
- National Cancer Institute [NIH P50-CA105009, NIH U01 CA-152990, NIH R21 CA-156021]
- Honorable Tina Brozman 'Tina's Wish' Foundation
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Robert and Debra First Fund
- Gamel Family Fund
- Canadian Institutes of Health Research Fellowship
- Kaleidoscope of Hope Foundation Young Investigator Research Grant
- National Health and Medical Research Council [APP 1042358]
The fallopian tube is now generally considered the dominant site of origin for high-grade serous ovarian carcinoma. However, the molecular pathogenesis of fallopian tube-derived serous carcinomas is poorly understood and there are few experimental studies examining the transformation of human fallopian tube cells. Prompted by recent genomic analyses that identified cyclin E1 (CCNE1) gene amplification as a candidate oncogenic driver in high-grade serous ovarian carcinoma, we evaluated the functional role of cyclin E1 in serous carcinogenesis. Cyclin E1 was expressed in early- and late-stage human tumor samples. In primary human fallopian tube secretory epithelial cells, cyclin E1 expression imparted malignant characteristics to untransformed cells if p53 was compromised, promoting an accumulation of DNA damage and altered transcription of DNA damage response genes related to DNA replication stress. Together, our findings corroborate the hypothesis that cyclin E1 dysregulation acts to drive malignant transformation in fallopian tube secretory cells that are the site of origin of high-grade serous ovarian carcinomas. (C)2013 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据