Document Detail

Evaluation of a luciferase-based reporter assay as a screen for inhibitors of estrogen-ERα-induced proliferation of breast cancer cells.
MedLine Citation:
PMID:  22498909     Owner:  NLM     Status:  MEDLINE    
Estrogens, acting through estrogen receptor α (ERα), stimulate breast cancer proliferation, making ERα an attractive drug target. Since 384-well format screens for inhibitors of proliferation can be challenging for some cells, inhibition of luciferase-based reporters is often used as a surrogate end point. To identify novel small-molecule inhibitors of 17β-estradiol (E(2))-ERα-stimulated cell proliferation, we established a cell-based screen for inhibitors of E(2)-ERα induction of an estrogen response element (ERE)(3)-luciferase reporter. Seventy-five "hits" were evaluated in tiered follow-up assays to identify where hits failed to progress and evaluate their effectiveness as inhibitors of E(2)-ERα-induced proliferation of breast cancer cells. Only 8 of 75 hits from the luciferase screen inhibited estrogen-induced proliferation of ERα-positive MCF-7 and T47D cells but not control ERα-negative MDA-MB-231 cells. Although 12% of compounds inhibited E(2)-ERα-stimulated proliferation in only one of the ERα-positive cell lines, 40% of compounds were toxic and inhibited growth of all the cell lines, and ~37% exhibited little or no ability to inhibit E(2)-ERα-stimulated cell proliferation. Representative compounds were evaluated in more detail, and a lead ERα inhibitor was identified.
Neal Andruska; Chengjian Mao; Mathew Cherian; Chen Zhang; David J Shapiro
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-12
Journal Detail:
Title:  Journal of biomolecular screening     Volume:  17     ISSN:  1552-454X     ISO Abbreviation:  J Biomol Screen     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-12     Completed Date:  2013-01-17     Revised Date:  2014-08-17    
Medline Journal Info:
Nlm Unique ID:  9612112     Medline TA:  J Biomol Screen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  921-32     Citation Subset:  IM    
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MeSH Terms
Biological Assay
Breast Neoplasms / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Screening Assays, Antitumor / methods*
Estradiol / metabolism
Estrogen Receptor alpha / antagonists & inhibitors*,  metabolism*
Gene Expression Regulation, Neoplastic
Genes, Reporter
High-Throughput Screening Assays / methods*
Response Elements
Grant Support
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/estrogen receptor alpha, human; 4TI98Z838E/Estradiol; EC 1.13.12.-/Luciferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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