Regulated ectopic expression of cyclin D1 induces transcriptional activation of the cdk inhibitor p21 gene without altering cell cycle progression Journal Article
| Authors: | Hiyama, H.; Iavarone, A.; LaBaer, J.; Reeves, S. A. |
| Article Title: | Regulated ectopic expression of cyclin D1 induces transcriptional activation of the cdk inhibitor p21 gene without altering cell cycle progression |
| Abstract: | Cyclin D1 plays a key regulatory role during the G1 phase of the cell cycle and its gene is amplified and overexpressed in many cancers. To address the relationship between cyclin D1 and other cell cycle regulatory proteins, we established human glioma and rodent fibroblast cell lines in which cyclin D1 expression could be regulated ectopically with tetracycline. In both of these cell lines, we found that ectopic expression of cyclin D1 in asynchronously growing cells was accompanied by increased levels of the p53 tumor suppressor protein and the cyclin/cdk inhibitor p21. Despite the induction of these cell cycle inhibitory proteins, cyclin D1-associated cdk kinase remained activated and the cells grew essentially like that of the parent cells. Although growth parameters were unchanged in these cells, morphological changes were clearly identifiable and anchorage independent growth was observed in NIH3T3 cells. In a first step toward elaborating the mechanism for cyclin D1-mediated induction of p21 gene expression we show that co-expression of E2F-1 and DP-1 can specifically transactivate the p21 promoter. In support of these findings and a direct effect of E2F on induction of p21 gene expression a putative E2F binding site was identified within the p21 promoter. In summary, our results demonstrate that ectopic expression of cyclin D1 can induce gene expression of the cdk inhibitor p21 through an E2F mechanism the consequences of which are not to growth arrest cells but possibly to stabilize cyclin D1/cdk function. |
| Keywords: | immunohistochemistry; controlled study; human cell; promoter region; dna-binding proteins; proto-oncogene proteins; nonhuman; glioma; animal cell; mouse; animals; cell cycle proteins; mice; cell cycle; cell division; gene amplification; models, biological; cell growth; protein p53; time factors; animalia; transcription factors; gene expression regulation; tumor suppressor gene; blotting, western; enzyme inhibitors; oncogene proteins; carrier proteins; transactivation; transcription; fibroblasts; tumor suppressor protein p53; base sequence; binding site; cell size; rodentia; cyclin-dependent kinase inhibitor p21; cyclin d1; cyclin-dependent kinases; cyclins; cyclin dependent kinase inhibitor; tetracycline; protein p21; cell cycle g1 phase; cell strain 3t3; p21; 3t3 cells; cyclin-dependent kinase 4; transcription factor dp1; e2f1 transcription factor; e2f; trans-activation (genetics); e2f transcription factors; humans; human; priority journal; article |
| Journal Title: | Oncogene |
| Volume: | 14 |
| Issue: | 21 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1997-05-29 |
| Start Page: | 2533 |
| End Page: | 2542 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1201080 |
| PUBMED: | 9191053 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
