Abstract
Estrogens stimulate proliferation of estrogen receptor positive MCF7 breast cancer cells while ant/estrogens signal a G0/G1 growth arrest. In MCF7 cells, arrest is mediated through the CDK inhibitors p21 and p27 and through a decrease in cyclin E/CDK2 kinase activity. We found that in MCF7 cells, overexpression of cyclin E partially abrogates a tamoxifen mediated growth arrest. Overexpression of cyclin E is accompanied by a decrease in the levels of RB and CDK inhibitor p21 but an increase in CDK inhibitor p27. Cyclin E overexpression also alters the composition of E2F transcription factor complexes. The E2F4/p107/cyclin E/CDK2 complex, a minor component in proliferating control cells that is absent in growth-arrested cells, is more abundant in both proliferating and tamoxifen treated cyclin E overexpressing cells. Conversely, levels of the quiescence associated E2F/p130 complex is not detected in these cells. Expression from the E2F dependant promoter is elevated in proliferating and tamoxifen treated cyclin E over-expressing cells. This study suggests that a modest overexpression of cyclin E abrogates the tamoxifen mediated growth arrest through modification of the RB/E2F pathway. Moreover, these results provide one explanation of why some cells that express the estrogen receptor may be unresponsive to antiestrogens.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4626-4634 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 21 |
| Issue number | 30 |
| DOIs | |
| State | Published - Jul 11 2002 |
Fingerprint
Keywords
- Breast cancer
- Cell cycle
- Cyclin E
- MCF7
- Tamoxifen
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest. / Dhillon, Navdeep K.; Mudryj, Maria.
In: Oncogene, Vol. 21, No. 30, 11.07.2002, p. 4626-4634.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest
AU - Dhillon, Navdeep K.
AU - Mudryj, Maria
PY - 2002/7/11
Y1 - 2002/7/11
N2 - Estrogens stimulate proliferation of estrogen receptor positive MCF7 breast cancer cells while ant/estrogens signal a G0/G1 growth arrest. In MCF7 cells, arrest is mediated through the CDK inhibitors p21 and p27 and through a decrease in cyclin E/CDK2 kinase activity. We found that in MCF7 cells, overexpression of cyclin E partially abrogates a tamoxifen mediated growth arrest. Overexpression of cyclin E is accompanied by a decrease in the levels of RB and CDK inhibitor p21 but an increase in CDK inhibitor p27. Cyclin E overexpression also alters the composition of E2F transcription factor complexes. The E2F4/p107/cyclin E/CDK2 complex, a minor component in proliferating control cells that is absent in growth-arrested cells, is more abundant in both proliferating and tamoxifen treated cyclin E overexpressing cells. Conversely, levels of the quiescence associated E2F/p130 complex is not detected in these cells. Expression from the E2F dependant promoter is elevated in proliferating and tamoxifen treated cyclin E over-expressing cells. This study suggests that a modest overexpression of cyclin E abrogates the tamoxifen mediated growth arrest through modification of the RB/E2F pathway. Moreover, these results provide one explanation of why some cells that express the estrogen receptor may be unresponsive to antiestrogens.
AB - Estrogens stimulate proliferation of estrogen receptor positive MCF7 breast cancer cells while ant/estrogens signal a G0/G1 growth arrest. In MCF7 cells, arrest is mediated through the CDK inhibitors p21 and p27 and through a decrease in cyclin E/CDK2 kinase activity. We found that in MCF7 cells, overexpression of cyclin E partially abrogates a tamoxifen mediated growth arrest. Overexpression of cyclin E is accompanied by a decrease in the levels of RB and CDK inhibitor p21 but an increase in CDK inhibitor p27. Cyclin E overexpression also alters the composition of E2F transcription factor complexes. The E2F4/p107/cyclin E/CDK2 complex, a minor component in proliferating control cells that is absent in growth-arrested cells, is more abundant in both proliferating and tamoxifen treated cyclin E overexpressing cells. Conversely, levels of the quiescence associated E2F/p130 complex is not detected in these cells. Expression from the E2F dependant promoter is elevated in proliferating and tamoxifen treated cyclin E over-expressing cells. This study suggests that a modest overexpression of cyclin E abrogates the tamoxifen mediated growth arrest through modification of the RB/E2F pathway. Moreover, these results provide one explanation of why some cells that express the estrogen receptor may be unresponsive to antiestrogens.
KW - Breast cancer
KW - Cell cycle
KW - Cyclin E
KW - MCF7
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=0037063172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037063172&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1205576
DO - 10.1038/sj.onc.1205576
M3 - Article
C2 - 12096339
AN - SCOPUS:0037063172
VL - 21
SP - 4626
EP - 4634
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 30
ER -