机构：[1]Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Blavatnik Institute, Harvard Medical School , Boston, MA, USA.[2]Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences &四川省人民医院[3] Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu, China.四川省人民医院
Basal-like triple-negative breast cancers frequently express high levels of c-Myc. This oncoprotein signals to the core cell cycle machinery by impinging on cyclin E. High levels of E-type cyclins (E1 and E2) are often seen in human triple-negative breast tumors. In the current study, we examined the requirement for E-type cyclins in the c-Myc-driven mouse model of breast cancer (MMTV-c-Myc mice). To do so, we crossed cyclin E1- (E1-/-) and E2- (E2-/-) deficient mice with MMTV-c-Myc animals, and observed the resulting cyclin E1-/-/MMTV-c-Myc and cyclin E2-/-/MMTV-c-Myc females for breast cancer incidence. We found that mice lacking cyclins E1 or E2 developed breast cancers like their cyclin Ewild-type counterparts. In contrast, further reduction of the dosage of E-cyclins in cyclin E1-/-E2+/-/MMTV-c-Myc and cyclin E1+/-E2-/-/MMTV-c-Myc animals significantly decreased the incidence of mammary carcinomas, revealing arole for E-cyclins in tumor initiation. We also observed that depletion of E-cyclins in human triple-negative breast cancer cell lines halted cell cycle progression, indicating that E-cyclins are essential for tumor cell proliferation. In contrast, we found that the catalytic partner of E-cyclins, the cyclin-dependent kinase 2 (CDK2), is dispensable for the proliferation of these cells. These results indicate that E-cyclins, but not CDK2, play essential and rate-limiting roles in driving the proliferation of c-Myc overexpressing breast cancer cells.
基金：
This work was supported by grants R01 CA202634 and P50 CA168504 (Project 1) from NIH to P.S., Yu Zhou and Yubin Zhou were supported by a fellowship from Sichuan Provincial People’s Hospital, Y. Zhang by a fellowship from China Scholarship Council, Y.G. is partially supported by R50 CA243769 from NIH and D. B. by a scholarship from the Studienstiftung des deutschen Volkes (German Academic Scholarship Foundation).
第一作者机构：[1]Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Blavatnik Institute, Harvard Medical School , Boston, MA, USA.[2]Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences &[3] Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu, China.
推荐引用方式(GB/T 7714)：
Zhou Yu,Geng Yan,Zhang Yujiao,et al.The requirement for cyclin E in c-Myc overexpressing breast cancers.[J].CELL CYCLE.2020,19(20):2589-2599.doi:10.1080/15384101.2020.1804720.
APA：
Zhou Yu,Geng Yan,Zhang Yujiao,Zhou Yubin,Chu Chen...&Sicinski Piotr.(2020).The requirement for cyclin E in c-Myc overexpressing breast cancers..CELL CYCLE,19,(20)
MLA：
Zhou Yu,et al."The requirement for cyclin E in c-Myc overexpressing breast cancers.".CELL CYCLE 19..20(2020):2589-2599
