دورية أكاديمية
The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors.
| العنوان: | The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors. |
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| المؤلفون: | Shen Q; Breast Center, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA., Uray IP, Li Y, Krisko TI, Strecker TE, Kim HT, Brown PH |
| المصدر: | Oncogene [Oncogene] 2008 Jan 10; Vol. 27 (3), pp. 366-77. Date of Electronic Publication: 2007 Jul 16. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002->: Basingstoke : Nature Publishing Group Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987- |
| مواضيع طبية MeSH: | Breast Neoplasms/*pathology , Cyclin D1/*antagonists & inhibitors , E2F Transcription Factors/*metabolism , Transcription Factor AP-1/*metabolism, Breast Neoplasms/genetics ; Cell Line, Tumor ; Cell Proliferation ; Chromatin Immunoprecipitation ; Cyclin D1/genetics ; Cyclin D1/metabolism ; Cyclins/genetics ; Cyclins/metabolism ; Down-Regulation ; E2F Transcription Factors/genetics ; E2F1 Transcription Factor/genetics ; E2F1 Transcription Factor/metabolism ; E2F2 Transcription Factor/genetics ; E2F2 Transcription Factor/metabolism ; E2F4 Transcription Factor/genetics ; E2F4 Transcription Factor/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Peptide Fragments/metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-jun/metabolism ; RNA, Messenger/antagonists & inhibitors ; RNA, Messenger/metabolism ; Transcription Factor AP-1/antagonists & inhibitors ; Transcription Factor DP1/metabolism |
| مستخلص: | The activating protein-1 (AP-1) transcription factor transduces growth signals through signal transduction pathways to the nucleus, leading to the expression of genes involved in growth and malignant transformation in many cell types. We have previously shown that overexpression of a dominant negative form of the cJun proto-oncogene, a cJun dominant negative mutant (Tam67), blocks AP-1 transcriptional activity, induces a G(1) cell cycle block and inhibits breast cancer cell growth in vitro and in vivo. We found that AP-1 blockade by Tam67 in MCF-7 breast cancer cells downregulates cyclin D1 transcriptional activity by at least two mechanisms: by suppressing transcription at the known AP-1 binding site (-934/-928) and by suppressing growth factor-induced expression through suppressing E2F activation at the E2F-responsive site (-726/-719). AP-1 blockade also led to reduced expression of E2F1 and E2F2, but not E2F4, at the mRNA and protein levels. Chromatin immunoprecipitation and supershift assays demonstrated that AP-1 blockade caused decreased binding of E2F1 protein to the E2F site in the cyclin D1 promoter. We also found that Tam67 suppressed the expression of the E2F1 dimerizing partner, DP1 and E2F-upregulated cell cycle genes (cyclins E, A, B and D3) and enhanced the expression of E2F-downregulated cell cycle genes (cyclins G(2) and I). Reduced expression of other E2F-regulated genes was also seen with AP-1 blockade and E2F suppression. Thus, the AP-1 factor regulates the expression of cyclin D and E2F (the latter in turn regulates E2F-downstream genes), leading to cell cycle progression and breast cancer cell proliferation. |
| المشرفين على المادة: | 0 (Cyclins) 0 (E2F Transcription Factors) 0 (E2F1 Transcription Factor) 0 (E2F1 protein, human) 0 (E2F2 Transcription Factor) 0 (E2F4 Transcription Factor) 0 (MAS1 protein, human) 0 (Peptide Fragments) 0 (Proto-Oncogene Mas) 0 (Proto-Oncogene Proteins c-jun) 0 (RNA, Messenger) 0 (TAM67 peptide) 0 (Transcription Factor AP-1) 0 (Transcription Factor DP1) 136601-57-5 (Cyclin D1) |
| تواريخ الأحداث: | Date Created: 20070720 Date Completed: 20080215 Latest Revision: 20211203 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1038/sj.onc.1210643 |
| PMID: | 17637753 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1476-5594 |
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| DOI: | 10.1038/sj.onc.1210643 |