ArticleThe American journal of pathology1998
Role of p27Kip1 and cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer.
Article in The American journal of pathology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 98 citations in OpenAlex.
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- FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy.Current medical science · 2022Article
- Identifying Novel Drug Targets by iDTPnd: A Case Study of Kinase Inhibitors.Genomics, proteomics & bioinformatics · 2021Article
- Discovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinoma.Molecular medicine (Cambridge, Mass.) · 2021Article
- Role of Xeroderma Pigmentosum Group D in Cell Cycle and Apoptosis in Cutaneous Squamous Cell Carcinoma A431 Cells.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- DNA methylation inhibitor causes cell growth retardation and gene expression changes in feline lymphoma cells.The Journal of veterinary medical science · 2017Article
- FKBP3 Promotes Proliferation of Non-Small Cell Lung Cancer Cells through Regulating Sp1/HDAC2/p27.Theranostics · 2017Article
- TMEM45B, up-regulated in human lung cancer, enhances tumorigenicity of lung cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Insights on Structural Characteristics and Ligand Binding Mechanisms of CDK2.International journal of molecular sciences · 2015Review
- Screening of cell cycle fusion proteins to identify kinase signaling networks.Cell cycle (Georgetown, Tex.) · 2015Article
- Tumor suppressors and cell-cycle proteins in lung cancer.Pathology research international · 2011Article
- A phase 1 study of SNS-032 (formerly BMS-387032), a potent inhibitor of cyclin-dependent kinases 2, 7 and 9 administered as a single oral dose and weekly infusion in patients with metastatic refractory solid tumors.Investigational new drugs · 2008Article
- Article
- Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
- RNA silencing of S-phase kinase-interacting protein 2 inhibits proliferation and centrosome amplification in lung cancer cells.Oncogene · 2005Article
- p27Kip1 is expressed in proliferating cells in its form phosphorylated on threonine 187.BMC clinical pathology · 2005Article
- The prognosis in spindle-cell sarcoma depends on the expression of cyclin-dependent kinase inhibitor p27(Kip1) and cyclin E.Cancer science · 2003Article
- Immunohistochemical expression of cyclin E in endometrial adenocarcinoma (endometrioid type) and its clinicopathological significance.Journal of cancer research and clinical oncology · 2003Article
- Loss of the cell cycle inhibitors p21(Cip1) and p27(Kip1) enhances tumorigenesis in knockout mouse models.Oncogene · 2002Article
- Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus - correlation with proliferation and clinicopathological parameters.British journal of cancer · 2002Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cell cycle is governed by a family of cyclin-dependent kinases (Cdks). Cdk2 forms a functional complex with cyclin E and plays a pivotal role in the regulation of G1/S transition. Cdk2 activity is negatively regulated by interactions with inhibitors. p27Kip1, one of the most potent inhibitors of Cdk2, was recently identified as a powerful negative prognostic marker in non-small cell lung cancer as well as in colorectal and breast cancer. In the present study, the expression of p27 and Ki-67 antigen in nonneoplastic and cancerous lung tissues was determined by immunohistochemistry. After establishing that the antibody-measured p27 labeling index was a good reflection of the level of p27 expression measured by Western blotting, we show that p27 labeling index is decreased in cancerous lung tissues, compared with nonneoplastic lung tissues, and exhibits a significant inverse relation to the proliferation marker Ki-67 antigen, detected with monoclonal antibody MIB-1. Consistent with these data, all cancerous lung tissues showed enhanced degradation activity of p27 compared with nonneoplastic lung tissues and, in addition, increased levels of the phosphorylated form of Cdk2, as determined with Western blot analysis. The H1 histone kinase activity associated with Cdk2 was also increased in non-small cell lung cancers. Statistical analysis showed that proliferative activity as measured by MIB-1 labeling index was highly correlated with Cdk2 activity (r = 0.767, P < 0.0015). These results suggest that p27 and Cdk2 may play an important role in the proliferation of non-small cell cancer.
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