Involvement of p27(KIP1) in G(1) arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody Journal Article
| Authors: | Wu, X.; Rubin, M.; Fan, Z.; DeBlasio, T.; Soos, T.; Koff, A.; Mendelsohn, J. |
| Article Title: | Involvement of p27(KIP1) in G(1) arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody |
| Abstract: | Activation of the cyclin dependent kinases (CDK4/CDK6 and CDK2) is required for G, phase progression and entry into S-phase. The activation of these kinases is regulated by checkpoints that monitor environmental and intracellular conditions. Progression into S-phase is controlled, in part, by the availability of growth factors, and we have investigated the relationship between growth factor availability and the activation of the CDK kinases. Blocking activation of epidermal growth factor (EGF) receptor tyrosine kinase with anti-EGF receptor monoclonal antibody (mAb) 225 induces G, phase cell cycle arrest in DiFi human colon adenocarcinoma cells. When DiFi cells are treated with mAb 225 for 24 h, we observe marked decreases in the activities of CDK2 kinase and cyclin E-associated CDK kinase which are not accompanied by reduced levels of cyclin E and CDK2 proteins. However, the amount of cyclin/CDK kinase inhibitor p27KIP1 increases in the mAb-treated cells and p27KIP1 is bound to CDK2 in increasing amounts. Immunodepletion of p27KIP1 removes an inhibitory activity from lysates of mAb-treated cells: the immunodepleted and heated lysates lose the capacity to inhibit cyclin E/CDK2 activity in an in vitro assay. The results suggest that GI arrest in the cell cycle induced by EGF receptor blockade involves p27KIP1. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; human cell; cell cycle protein; metabolism; cell cycle proteins; cell cycle; cell cycle s phase; cell growth; epidermal growth factor receptor; receptor, epidermal growth factor; enzyme activation; drug effect; tumor cells, cultured; enzyme inhibitor; enzyme activity; monoclonal antibody; immunology; antibodies, monoclonal; drug antagonism; cell culture; cyclin dependent kinase inhibitor 1b; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; cell cycle arrest; tumor suppressor protein; cyclin-dependent kinases; cyclins; cyclin dependent kinase; growth factor; colon adenocarcinoma; cell cycle g1 phase; g1 phase; cyclin e; epidermal growth factor receptor kinase; mab; p27kip1; enzyme stability; microtubule-associated proteins; microtubule associated protein; egf receptor; heat; cdks; humans; human; priority journal; article; monoclonal antibody 225 |
| Journal Title: | Oncogene |
| Volume: | 12 |
| Issue: | 7 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1996-04-04 |
| Start Page: | 1397 |
| End Page: | 1403 |
| Language: | English |
| PUBMED: | 8622855 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
