| Added by | standudu |
|---|---|
| Last modified by | jacques.colinge |
| Group name | EquipeJC |
| Item Type | Journal Article |
| Title | Cell-Cycle Regulation Accounts for Variability in Ki-67 Expression Levels |
| Creator | Sobecki et al. |
| Author | Michal Sobecki |
| Author | Karim Mrouj |
| Author | Jacques Colinge |
| Author | François Gerbe |
| Author | Philippe Jay |
| Author | Liliana Krasinska |
| Author | Vjekoslav Dulic |
| Author | Daniel Fisher |
| Abstract | The cell proliferation antigen Ki-67 is widely used in cancer histopathology, but estimations of Ki-67 expression levels are inconsistent and understanding of its regulation is limited. Here we show that cell-cycle regulation underlies variable Ki-67 expression in all situations analyzed, including nontransformed human cells, normal mouse intestinal epithelia and adenomas, human cancer cell lines with or without drug treatments, and human breast and colon cancers. In normal cells, Ki-67 was a late marker of cell-cycle entry; Ki-67 mRNA oscillated with highest levels in G2while protein levels increased throughout the cell cycle, peaking in mitosis. Inhibition of CDK4/CDK6 revealed proteasome-mediated Ki-67 degradation in G1After cell-cycle exit, low-level Ki-67 expression persisted but was undetectable in fully quiescent differentiated cells or senescent cells. CDK4/CDK6 inhibitionin vitroand in tumors in mice caused G1cell-cycle arrest and eliminated Ki-67 mRNA in RB1-positive cells but had no effect in RB1-negative cells, which continued to proliferate and express Ki-67. Thus, Ki-67 expression varies due to cell-cycle regulation, but it remains a reliable readout for effects of CDK4/CDK6 inhibitors on cell proliferation.Cancer Res; 77(10); 2722-34. ©2017 AACR. |
| Publication | Cancer Research |
| Volume | 77 |
| Issue | 10 |
| Pages | 2722-2734 |
| Date | May 15, 2017 |
| Journal Abbr | Cancer Res. |
| Language | eng |
| DOI | 10.1158/0008-5472.CAN-16-0707 |
| ISSN | 1538-7445 |
| Library Catalog | PubMed |
| Extra | PMID: 28283655 |
| Tags | Animals, Antineoplastic Agents, arc, Biomarkers, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Cell Survival, Cluster Analysis, Female, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Immunohistochemistry, Intestinal Mucosa, Ki-67 Antigen, Mice, Mice, Knockout, original, Xenograft Model Antitumor Assays |
| Date Added | 2018/02/28 - 16:51:52 |
| Date Modified | 2021/09/07 - 08:37:48 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
