The requirement for cyclin E in c-Myc overexpressing breast cancers
Year: 2020
Type: dataset
Abstract: 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.
Source: Figshare
Authors: Zhou, Yu, Geng, Yan, Zhang, Yujiao, Zhou, Yubin, Chu, Chen, Sharma, Samanta, Fassl, Anne, Butter, Deborah, Sicinski, Piotr
Institutions: Yangtze University, Xiamen University, Jilin University, Chinese Academy of Medical Sciences & Peking Union Medical College, Huazhong Agricultural University, Peking Union Medical College Hospital, Hebei GEO University, Hebei North University, Sichuan University, Second Affiliated Hospital of Xi'an Jiaotong University, Tongji University, Guangdong Medical College, Texas A&M University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4394314890