Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27(KIP1) and induces G(1) arrest in prostatic cancer cell line DU145 Journal Article
| Authors: | Peng, D.; Fan, Z.; Lu, Y.; DeBlasio, T.; Scher, H.; Mendelsohn, J. |
| Article Title: | Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27(KIP1) and induces G(1) arrest in prostatic cancer cell line DU145 |
| Abstract: | Autocrine production of transforming growth factor α and overexpression of the epidermal growth factor receptor (EGFR) may contribute to androgen-independent prostatic cancer growth at both primary and metastatic sites. Previously, we showed that human EGFR-blocking monoclonal antibody mAb225 inhibited the growth of DU145 human prostatic cancer cells. Here we explore the hypothesis that mAb225 may act by interfering with cell cycle traversal in these cells. Treatment with mAb225 induced G1 arrest, which was accompanied by a marked decrease in CDK2-, cyclin A-, and cyclin E-associated histone H1 kinase activities, and a sustained increase in cell cycle inhibitor p27(KIP1). The increased p27(KIP1) levels were attributable to elevation of both transcription and translation. CDK2 associated with p27(KIP1) was increased in mAb225-treated DU145 cells. The retinoblastoma- related protein p130 remained hypophosphorylated in these retinoblastoma- negative cells. These studies demonstrate that the antiproliferative effect of EGFR blockade in DU145 cells may be mediated by up-regulation of p27(KIP1) at both the mRNA and protein levels. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; human cell; cell proliferation; cell cycle proteins; cell division; enzyme inhibition; epidermal growth factor receptor; receptor, epidermal growth factor; cancer cell culture; tumor cells, cultured; enzyme activity; monoclonal antibody; prostate cancer; prostatic neoplasms; gene expression regulation; antibodies, monoclonal; messenger rna; protein-serine-threonine kinases; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; immunoprecipitation; immunoblotting; cycline; cyclin-dependent kinases; cyclin a; cyclin dependent kinase; cell cycle phase; retinoblastoma protein; cell cycle g1 phase; g1 phase; enzyme assay; growth inhibition; northern blotting; cyclin-dependent kinase 2; microtubule-associated proteins; receptor antibody; monolayer culture; histone h1; cdc2-cdc28 kinases; humans; human; male; priority journal; article; protamine kinase |
| Journal Title: | Cancer Research |
| Volume: | 56 |
| Issue: | 16 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1996-08-15 |
| Start Page: | 3666 |
| End Page: | 3669 |
| Language: | English |
| PUBMED: | 8706005 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
