Search Results
You are looking at 1 - 1 of 1 items for
- Author: K Antrobus x
- Refine by access: All content x
Search for other papers by J G Moggs in
Google Scholar
PubMed
Search for other papers by T C Murphy in
Google Scholar
PubMed
Search for other papers by F L Lim in
Google Scholar
PubMed
Search for other papers by D J Moore in
Google Scholar
PubMed
Search for other papers by R Stuckey in
Google Scholar
PubMed
Search for other papers by K Antrobus in
Google Scholar
PubMed
Search for other papers by I Kimber in
Google Scholar
PubMed
Search for other papers by G Orphanides in
Google Scholar
PubMed
Estrogen receptor (ER)-negative breast carcinomas do not respond to hormone therapy, making their effective treatment very difficult. The re-expression of ERα in ER-negative MDA-MB-231 breast cancer cells has been used as a model system, in which hormone-dependent responses can be restored. Paradoxically, in contrast to the mitogenic activity of 17β-estradiol (E2) in ER-positive breast cancer cells, E2 suppresses proliferation in ER-negative breast cancer cells in which ERα has been re-expressed. We have used global gene expression profiling to investigate the mechanism by which E2 suppresses proliferation in MDA-MB-231 cells that express ERα through adenoviral infection. We show that a number of genes known to promote cell proliferation and survival are repressed by E2 in these cells. These include genes encoding the anti-apoptosis factor SURVIVIN, positive cell cycle regulators (CDC2, CYCLIN B1, CYCLIN B2, CYCLIN G1, CHK1, BUB3, STK6, SKB1, CSE1 L) and chromosome replication proteins (MCM2, MCM3, FEN1, RRM2, TOP2A, RFC1). In parallel, E2-induced the expression of the negative cell cycle regulators KIP2 and QUIESCIN Q6, and the tumour-suppressor genes E-CADHERIN and NBL1. Strikingly, the expression of several of these genes is regulated in the opposite direction by E2 compared with their regulation in ER-positive MCF-7 cells. Together, these data suggest a mechanism for the E2-dependent suppression of proliferation in ER-negative breast cancer cells into which ERα has been reintroduced.