K-ras modulates the cell cycle via both positive and negative regulatory pathways Journal Article
| Authors: | Fan, J.; Bertino, J. R. |
| Article Title: | K-ras modulates the cell cycle via both positive and negative regulatory pathways |
| Abstract: | The effect of activated human K-ras on cell cycle proteins was studied by use of a stable MCF-7 transfectant expressing inducible activated K-ras under the control of a tetracycline (Tet)-responsive promoter. Induction of activated K-ras by Tet withdrawal accelerated cell growth and entry into S-phase. To understand the mechanism(s) by which activated K-ras exerts its effect on the cell cycle, expression of both cell cycle stimulatory proteins as well as cell cycle inhibitors was examined. Upon induction of activated K-ras, several cell cycle stimulators were up-regulated, including cyclins A, D3, and E, and the E2F family of transcription factors, which was accompanied by increased cyclin A-associated kinase activity and E2F transcriptional activity, respectively. Up-regulation of cyclin A occurred at the transcriptional level and in a serum-dependent manner. Furthermore, induction of activated K-ras down-regulated p27(Kip1) and up-regulated p53. Up-regulation of p53 was correlated with enhanced p53 transactivation and accompanied by up-regulation of p21(Waf1) and Gadd 45, two p53 effecters and negative cell cycle regulators. In addition, activated K-ras upregulates bcl-2 but has no effect on bax or bcl-x expression. Taken together, these data indicate that activated K-ras affects the cell cycle by modulating both positive and negative cell cycle regulatory pathways. |
| Keywords: | human cell; dna-binding proteins; proto-oncogene proteins; adenocarcinoma; proteins; cell cycle protein; cell cycle proteins; cell cycle; cell division; cell growth; bcl-x protein; breast neoplasms; protein p53; time factors; transcription factors; gene expression regulation; oncogene; enzyme inhibitors; intracellular signaling peptides and proteins; carrier proteins; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; transactivation; tumor suppressor protein p53; ras protein; ras proteins; cyclin-dependent kinase inhibitor p21; oncogene k ras; cyclins; cell cycle phase; proto-oncogene proteins c-bcl-2; ras; s phase; gene regulation; microtubule-associated proteins; transcription factor dp1; bcl-2-associated x protein; e2f transcription factors; humans; human; female; priority journal; article; mink cell focus-forming virus |
| Journal Title: | Oncogene |
| Volume: | 14 |
| Issue: | 21 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1997-05-29 |
| Start Page: | 2595 |
| End Page: | 2607 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1201105 |
| PUBMED: | 9191059 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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