Cell Cycle Dependent Regulation of Human Progesterone Receptor in Breast Cancer

2004 ◽  
Author(s):  
Lisa K. Mullany ◽  
Carol A. Lange
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Progesterone Receptor ◽  
Human Progesterone Receptor ◽  
Cycle Dependent

scholarly journals Human Progesterone Receptor Displays Cell Cycle-Dependent Changes in Transcriptional Activity

2005 ◽  
Vol 25 (8) ◽  
pp. 2885-2898 ◽  
Author(s):  
Ramesh Narayanan ◽  
Dean P. Edwards ◽  
Nancy L. Weigel
Keyword(s):  
Cell Cycle ◽  
Progesterone Receptor ◽  
Transcriptional Activity ◽  
Trichostatin A ◽  
S Phase ◽  
Primary Defect ◽  
M Phase ◽  
Tumor Virus ◽  
Human Progesterone Receptor ◽  
Cycle Dependent

ABSTRACT The human progesterone receptor (PR) contains multiple Ser-Pro phosphorylation sites that are potential substrates for cyclin-dependent kinases, suggesting that PR activity might be regulated during the cell cycle. Using T47D breast cancer cells stably transfected with an mouse mammary tumor virus (MMTV) chloramphenicol acetyltransferase reporter (Cat0) synchronized in different phases of the cell cycle, we found that PR function and phosphorylation is remarkably cell cycle dependent, with the highest activity in S phase. Although PR expression was reduced in the G2/M phase, the activity per molecule of receptor was markedly reduced in both G1 and G2/M phases compared to the results seen with the S phase of the cell cycle. Although PR is recruited to the MMTV promoter equivalently in the G1 and S phases, recruitment of SRC-1, SRC-3, and, consequently, CBP is reduced in G1 phase despite comparable expression levels of SRC-1 and SRC-3. In G2/M phase, site-specific phosphorylation of PR at Ser162 and at Ser294, a site previously reported to be critical for transcriptional activity and receptor turnover, was abolished. Treatment with the histone deacetylase inhibitor trichostatin A elevated G1 and G2/M activity to that of the S phase, indicating that the failure to recruit sufficient levels of active histone acetyltransferase is the primary defect in PR-mediated transactivation.

scholarly journals Progesterone Receptor–Cyclin D1 Complexes Induce Cell Cycle–Dependent Transcriptional Programs in Breast Cancer Cells

2014 ◽  
Vol 28 (4) ◽  
pp. 442-457 ◽  
Author(s):  
Gwen E. Dressing ◽  
Todd P. Knutson ◽  
Matthew J. Schiewer ◽  
Andrea R. Daniel ◽  
Christy R. Hagan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Progesterone Receptor ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cycle Dependent

Cell-cycle-dependent expression of the large Ca2+-activated K+ channels in breast cancer cells

2004 ◽  
Vol 316 (1) ◽  
pp. 244-251 ◽  
Author(s):  
Halima Ouadid-Ahidouch ◽  
Morad Roudbaraki ◽  
Ahmed Ahidouch ◽  
Philippe Delcourt ◽  
Natalia Prevarskaya
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
K Channels ◽  
Cycle Dependent

PPARr agonist, troglitazone induce growth arrest and apoptosis in MDA-MB-231 human breast cancer cell

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13155-13155
Author(s):  
J. Park ◽  
Y. Lee ◽  
H. Yu ◽  
M. Han ◽  
B. Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Human Breast Cancer ◽  
Kinase Inhibitors ◽  
Growth Arrest ◽  
Ppar Gamma ◽  
G1 Arrest ◽  
Human Breast ◽  
Ppar Γ ◽  
Cycle Dependent

13155 Background: Estrogen receptor (ER)-negative breast carcinomas do not respond to hormone therapy, making their effective treatment very difficult. It is recently reported that peroxisome proliferator-activated receptor-gamma (PPAR-γ) has become a potential target for the prevention and treatment of human cancer. Therefore, PPAR-γ agonist, troglitazone has been extensively studied as a chemopreventive or therapeutic agent in several types of cancer. The purpose of this study was to assess whether troglitazone (TRO) would induce cell growth arrest and apoptosis in MDA-MB-231 (ER-negative) human breast cancer cells. Methods: Cytostatic/cytotoxic effects of troglitazone were measured with MTT assay. The cell cycle distribution was evaluated with flow cytometer. The expression of cyclin-dependent kinase inhibitors, p21, p27, and cell cycle dependent kinases was measured with Western blotting. Apoptotic cells were determined by Hoechst staining and TUNEL assay. Results: Troglitazone inhibited cell proliferation by inducing 65% G0/G1 arrest after 48 h. Accumulation of cells in G0/G1 was accompanied by a decrease of Rb protein phosphorylation associated with reduced activities of cell cycle dependent kinases (CDKs) such as cdk2 and cyclin D. Troglitazone increased the expression cyclin kinase inhibitors, p21 and p27 as MDA-MB-231 cell underwent G0/G1 arrest. Apoptotic effect by troglitazone demonstrated that apoptotic cells elevated from 2.5-fold of the control level at 10 uM, to 3.6-fold at 50 uM and to 4.7-fold at 75 uM. Conclusion: These results indicate that activation of PPAR-gamma with troglitazone induces apoptosis through cell cycle inhibition in estrogen receptor-negative breast cancer cell MDA-MB-231. PPAR-gamma therefore represents a putative molecular target for chemopreventive therapy or inhibition of breast cancer growth. No significant financial relationships to disclose.

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