2. Academic Validation
  3. The G1 phase optical reporter serves as a sensor of CDK4/6 inhibition in vivo

The G1 phase optical reporter serves as a sensor of CDK4/6 inhibition in vivo

  • Int J Biol Sci. 2021 Jan 31;17(3):728-741. doi: 10.7150/ijbs.52101.
Cuiping Guo 1 2,  Yuxian Guo 1 3,  Jingjing Liu 4 5,  Yiyang Gao 4 5,  Min Wei 4 5,  Ruijun Zhao 1,  Min Chen 5 6,  Guojun Zhang 4 5 6
Affiliations

Affiliations

  • 1 The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China.
  • 2 Guangdong Provincial Key Laboratory for Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, China.
  • 3 Present address: Department of Thyroid and Breast Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
  • 4 Cancer Center & Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
  • 5 Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, China.
  • 6 Clinical Central Research Core and Key Laboratory for Endocrine-Related Cancer Precision Medicine of Xiamen, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China.
PMID: 33767584 DOI: 10.7150/ijbs.52101
Abstract

Visualization of cell-cycle G1 phase for monitoring the early response of cell cycle specific drug remains challenging. In this study, we developed genetically engineered bioluminescent reporters by fusing full-length cyclin E to the C-terminal luciferase (named as CycE-Luc and CycE-Luc2). Next, HeLa cell line or an ER-positive breast Cancer cell line MCF-7 was transfected with these reporters. In cellular assays, the bioluminescent signal of CycE-Luc and CycE-Luc2 was accumulated in the G1 phase and decreased after exiting from the G1 phase. The expression of CycE-Luc and CycE-Luc2 fusion protein was regulated in a cell cycle-dependent manner, which was mediated by Proteasome ubiquitination and degradation. Next, our in vitro and in vivo experiment confirmed that the cell cycle arrested by anti-cancer agents (palbociclib or 5-FU) was monitored quantitatively and dynamically by bioluminescent imaging of these reporters in a real-time and non-invasive manner. Thus, these optical reporters could reflect the G1 phase alternation of cell cycle, and might become a future clinically translatable approach for predicting and monitoring response to palbociclib in patients with ER-positive breast Cancer.

Keywords

CDK4/6; bioluminescence; cyclin E; non-invasive molecular imaging; the G1 phase of the cell cycle.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-50767
    99.94%, CDK4/6 Inhibitor
    CDK