التفاصيل البيبلوغرافية
| العنوان: |
Epidermal growth factor-mediated T-cell factor/lymphoid enhancer factor transcriptional activity is essential but not sufficient for cell cycle progression in nontransformed mammary epithelial cells |
| المؤلفون: |
Graham, Nicholas A., Asthagiri, Anand R. |
| المصدر: |
Journal of Biological Chemistry, 279(22), 23517-23524, (2004-05-28) |
| بيانات النشر: |
American Society for Biochemistry and Molecular Biology |
| سنة النشر: |
2004 |
| المجموعة: |
Caltech Authors (California Institute of Technology) |
| مصطلحات موضوعية: |
GLYCOGEN-SYNTHASE KINASE-3, ACTIVATED PROTEIN-KINASE, COLON-CARCINOMA CELLS, BETA-CATENIN PATHWAY, E-CADHERIN, NEOPLASTIC TRANSFORMATION, NUCLEAR TRANSLOCATION, CANCER-CELLS, EXPRESSION, INHIBITION |
| الوصف: |
Because beta-catenin target genes such as cyclin D1 are involved in cell cycle progression, we examined whether beta-catenin has a more pervasive role in normal cell proliferation, even upon stimulation by non-Wnt ligands. Here, we demonstrate that epidermal growth factor (EGF) stimulates T-cell factor/lymphoid enhancer factor (Tcf/Lef) transcriptional activity in nontransformed mammary epithelial cells (MCF-10A) and that its transcriptional activity is essential for EGF-mediated progression through G(1)/S phase. Thus, expression of dominant-negative Tcf4 blocks EGF-mediated Tcf/Lef transcriptional activity and bromodeoxyuridine uptake. In fact, the importance of EGF-mediated Tcf/Lef transcriptional activity for cell cycle progression may lie further upstream at the G(1)/S phase transition. We demonstrate that dominant-negative Tcf4 inhibits a reporter of cyclin D1 promoter activity in a dose-dependent manner. Importantly, dominant-negative Tcf4 suppresses EGF- mediated cell cycle activity specifically by thwarting EGF- mediated Tcf/Lef transcriptional activity, not by broader effects on EGF signaling. Thus, although expression of dominant-negative Tcf4 blocks EGF- mediated TOPFLASH activation, it has no effect on either EGF receptor or ERK phosphorylation, further underscoring the fact that Tcf/ Lef-mediated transcription is essential for cell cycle progression, even when other pro-mitogenic signals are at normal levels. Yet, despite its essential role, Tcf/Lef transcriptional activity alone is not sufficient for cell cycle progression. Serum also stimulates Tcf/ Lef transcriptional activation in MCF-10A cells but is unable to promote DNA synthesis. Taken together, our data support a model wherein EGF promotes Tcf/ Lef transcriptional activity, and this signal is essential but not sufficient for cell cycle activity. ; © 2004 the American Society for Biochemistry and Molecular Biology. Received for publication, December 23, 2003, and in revised form, March 2, 2004. Published, JBC Papers in Press, March 16, ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://doi.org/10.1074/jbc.M314055200Test; oai:authors.library.caltech.edu:jtzx7-hf853; eprintid:7086; resolverid:CaltechAUTHORS:GRAjbc04 |
| DOI: |
10.1074/jbc.M314055200 |
| الإتاحة: |
https://doi.org/10.1074/jbc.M314055200Test |
| حقوق: |
info:eu-repo/semantics/openAccess ; Other |
| رقم الانضمام: |
edsbas.C8BC7041 |
| قاعدة البيانات: |
BASE |
