{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(47)"],"submitter":["Iida M"],"pubmed_abstract":["Although cyclin-dependent kinase (CDK) 4/6 inhibitors have exhibited remarkable results for patients with estrogen receptor (ER)-positive breast cancer in clinical trials, the mechanism of CDK4/6 inhibitor resistance remains unclear. Thus, this study aimed to investigate the mechanism of CDK4/6 inhibitor resistance using two CDK4/6 inhibitor resistant breast cancer cell lines. We established CDK6 overexpressed cell lines (MCF7-C6) from MCF-7 cells using the stably transfected CDK6 expression vector. Additionally, acquired ribociclib-resistant (RIBR) cell lines were created using ER-positive hormone-resistant cell lines by long-term exposure to ribociclib. CDK6 overexpression and the knockdown of CDK4 experiments highlight the significance of high levels of CDK4 and low levels of CDK6 in CDK4/6 inhibitor sensitivity. Moreover, RIBR cell lines did not exhibit incremental CDK6 compared with ER-positive hormone-resistant cell lines. In MCF7-C6 and RIBR cell lines, p21 levels decreased, and p21 levels were proportional to CDK4/6 inhibitor sensitivity. This study suggests that overexpression of CDK6 is one of the many possible mechanisms of resistance to CDK4/6 inhibitors. Furthermore, p21 levels have the potential to serve as a marker for CDK4/6 inhibitors independent of the resistance mechanism."],"journal":["Oncotarget"],"pagination":["4907-4918"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6690670"],"repository":["biostudies-literature"],"pubmed_title":["The p21 levels have the potential to be a monitoring marker for ribociclib in breast cancer."],"pmcid":["PMC6690670"],"pubmed_authors":["Niwa T","Iida M","Nakamura M","Hayashi SI","Ohuchi N","Tokuda E","Ishida T","Toyosawa D"],"additional_accession":[]},"is_claimable":false,"name":"The p21 levels have the potential to be a monitoring marker for ribociclib in breast cancer.","description":"Although cyclin-dependent kinase (CDK) 4/6 inhibitors have exhibited remarkable results for patients with estrogen receptor (ER)-positive breast cancer in clinical trials, the mechanism of CDK4/6 inhibitor resistance remains unclear. Thus, this study aimed to investigate the mechanism of CDK4/6 inhibitor resistance using two CDK4/6 inhibitor resistant breast cancer cell lines. We established CDK6 overexpressed cell lines (MCF7-C6) from MCF-7 cells using the stably transfected CDK6 expression vector. Additionally, acquired ribociclib-resistant (RIBR) cell lines were created using ER-positive hormone-resistant cell lines by long-term exposure to ribociclib. CDK6 overexpression and the knockdown of CDK4 experiments highlight the significance of high levels of CDK4 and low levels of CDK6 in CDK4/6 inhibitor sensitivity. Moreover, RIBR cell lines did not exhibit incremental CDK6 compared with ER-positive hormone-resistant cell lines. In MCF7-C6 and RIBR cell lines, p21 levels decreased, and p21 levels were proportional to CDK4/6 inhibitor sensitivity. This study suggests that overexpression of CDK6 is one of the many possible mechanisms of resistance to CDK4/6 inhibitors. Furthermore, p21 levels have the potential to serve as a marker for CDK4/6 inhibitors independent of the resistance mechanism.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2025-04-05T00:13:58.531Z","creation":"2019-08-28T07:02:50Z"},"accession":"S-EPMC6690670","cross_references":{"pubmed":["31448056"],"doi":["10.18632/oncotarget.27127"]}}