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Elevated expression of the estrogen receptor prevents the down‐regulation of p21 Waf1/Cip1 in hormone dependent breast cancer cells
Author(s) -
Zhao Helen,
Yu Jenny,
Peltier Cheryl P.,
Davie James R.
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20218
Subject(s) - estrogen receptor , cyclin d1 , cyclin dependent kinase , estrogen , cyclin dependent kinase 2 , estrogen receptor alpha , cdk inhibitor , cell cycle , cyclin d , cyclin e , cancer cell , cancer research , cyclin , estrogen receptor beta , chemistry , biology , microbiology and biotechnology , endocrinology , cell , protein kinase a , kinase , breast cancer , cancer , biochemistry , genetics
Expression of an estrogen receptor α (ER) transgene in hormone independent breast cancer and normal breast epithelial cells arrests cell cycling when estradiol is added. Although endogenously expressed ER does not typically affect estradiol‐induced cell cycling of hormone dependent breast cancer cells, we observed that elevated expression of a green fluorescent protein fused to ER (GFP‐ER) hindered entry of estrogen treated MCF‐7 cells into S phase of the cell cycle. In analyses of key cell‐cycle regulating proteins, we observed that GFP‐ER expression had no affect on the protein levels of cyclin D1, cyclin E, or p27, a cyclin dependent kinase (Cdk) inhibitor. However, at 24 h, p21 (Waf1, Cip1; a Cdk2 inhibitor) protein remained elevated in the high GFP‐ER expressing cells but not in non‐GFP‐ER expressing cells. Elevated expression of p21 inhibited Cdk2 activity, preventing cells from entering S phase. The results show that elevated levels of ER prevented the down‐regulation of p21 protein expression, which is required for hormone responsive cells to enter S phase. © 2004 Wiley‐Liss, Inc.