scholarly journals Insulin/Insulin-like Growth Factor-I and Estrogen Cooperate to Stimulate Cyclin E-Cdk2 Activation and Cell Cycle Progression in MCF-7 Breast Cancer Cells through Differential Regulation of Cyclin E and p21WAF1/Cip1

2001 ◽  
Vol 276 (28) ◽  
pp. 25823-25833 ◽  
Author(s):  
Angela Lai ◽  
Boris Sarcevic ◽  
Owen W. J. Prall ◽  
Robert L. Sutherland
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Growth Factor ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Differential Regulation ◽  
Cycle Progression ◽  
Factor I ◽  
Mcf 7

scholarly journals Regulation of cell cycle and cyclins by 16alpha-hydroxyestrone in MCF-7 breast cancer cells

2001 ◽  
Vol 27 (3) ◽  
pp. 293-307 ◽  
Author(s):  
JS Lewis ◽  
TJ Thomas ◽  
CM Klinge ◽  
MA Gallo ◽  
T Thomas
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Dna Synthesis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Fold Increase ◽  
Cycle Progression ◽  
Synchronized Cells ◽  
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It has been suggested that alterations in estradiol (E(2)) metabolism, resulting in increased production of 16alpha-hydroxyestrone (16alpha-OHE(1)), is associated with an increased risk of breast cancer. In the present study, we examined the effects of 16alpha-OHE(1)on DNA synthesis, cell cycle progression, and the expression of cell cycle regulatory genes in MCF-7 breast cancer cells. G(1) synchronized cells were treated with 1 to 25 nM 16alpha-OHE(1) for 24 and 48 h. [(3)H]Thymidine incorporation assay showed that 16alpha-OHE(1) caused an 8-fold increase in DNA synthesis compared with that of control cells, whereas E(2) caused a 4-fold increase. Flow cytometric analysis of cell cycle progression also demonstrated the potency of 16alpha-OHE(1) in stimulating cell growth. When G(1) synchronized cells were treated with 10 nM 16alpha-OHE(1) for 24 h, 62+/-3% of cells were in S phase compared with 14+/-3% and 52+/-2% of cells in the control and E(2)-treated groups respectively. In order to explore the role of 16alpha-OHE(1) in cell cycle regulation, we examined its effects on cyclins (D1, E, A, B1), cyclin dependent kinases (Cdk4, Cdk2), and retinoblastoma protein (pRB) using Western and Northern blot analysis. Treatment of cells with 10 nM 16alpha-OHE(1) resulted in 4- and 3-fold increases in cyclin D1 and cyclin A, respectively, at the protein level. There was also a significant increase in pRB phosphorylation and Cdk2 activation. In addition, transient transfection assay using an estrogen response element-driven luciferase reporter vector showed a 15-fold increase in estrogen receptor-mediated transactivation compared with control. These results show that 16alpha-OHE(1) is a potent estrogen capable of accelerating cell cycle kinetics and stimulating the expression of cell cycle regulatory proteins.

scholarly journals Review of: c-Myc suppresses p21WAF1/CIP1expression during oestrogen signalling and antioestrogen resistance in human breast cancer cells

2006 ◽  
Vol 9 (5) ◽  
pp. 1-4
Author(s):  
C. M. McNeil ◽  
E. A. Musgrove
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Human Breast ◽  
Cycle Progression ◽  
Oestrogen Treatment ◽  
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Citation of original article:S. Mukherjee, S. E. Conrad.Journal of Biological Chemistry2005;280: 17616–17625.Abstract of the original article:Oestrogen rapidly induces expression of the proto-oncogene c-Myc. c-Myc is required for oestrogen-stimulated proliferation of breast cancer cells, and deregulated c-Myc expression has been implicated in antioestrogen resistance. In this report, we investigate the mechanism(s) by which c-Myc mediates oestrogen-stimulated proliferation and contributes to cell cycle progression in the presence of antioestrogen. The MCF-7 cell line is a model of oestrogen-dependent, antioestrogen-sensitive human breast cancer. Using stable MCF-7 derivatives with inducible c-Myc expression, we demonstrated that in antioestrogen-treated cells, the elevated mRNA and protein levels of p21WAF1/CIP1, a cell cycle inhibitor, decreased upon either c-Myc induction or oestrogen treatment. Expression of p21 blocked c-Myc-mediated cell cycle progression in the presence of antioestrogen, suggesting that the decrease in p21WAF1/CIP1is necessary for this process. Using RNA interference to suppress c-Myc expression, we further established that c-Myc is required for oestrogen-mediated decreases in p21WAF1/CIP1. Finally, we observed that neither c-Myc nor p21WAF1/CIP1is regulated by oestrogen or antioestrogen in an antioestrogen-resistant MCF-7 derivative. The p21 levels in the antioestrogen-resistant cells increased when c-Myc expression was suppressed, suggesting that loss of p21 regulation was a consequence of constitutive c-Myc expression. Together, these studies implicate p21WAF1/CIP1as an important target of c-Myc in breast cancer cells and provide a link between oestrogen, c-Myc, and the cell cycle machinery. They further suggest that aberrant c-Myc expression, which is frequently observed in human breast cancers, can contribute to antioestrogen resistance by altering p21WAF1/CIP1regulation.

Retinoic Acid Inhibition of Cell Cycle Progression in MCF-7 Human Breast Cancer Cells

1997 ◽  
Vol 234 (2) ◽  
pp. 293-299 ◽  
Author(s):  
Wei-Yong Zhu ◽  
Carol S. Jones ◽  
Andras Kiss ◽  
Karen Matsukuma ◽  
Sonal Amin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Retinoic Acid ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Cycle Progression ◽  
Mcf 7
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