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Series GSE132343 Query DataSets for GSE132343
Status Public on Dec 10, 2019
Title Suppression of FOXM1 Activities and Breast Cancer Growth in Vitro and in Vivo by a New Class of Compounds
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The transcription factor FOXM1 is up-regulated and overexpressed in aggressive, therapy-resistant forms of hormone receptor-positive and triple negative breast cancers, and is associated with less good patient survival. FOXM1 pathway signaling is also a key driver in other aggressive cancers, including those in prostate, lung, ovary, and gastrointestinal tract. Therefore, our goal has been to identify compounds effective in suppressing FOXM1 activity and breast cancer proliferation, and displaying good potency and pharmacokinetic properties for in vivo antitumor efficacy. In this report, we describe our studies on the FOXM1 targeting activities of 1,1-diarylethylene mono- and diamine compounds and their methiodide salts in cell-free, cell-based, and in vivo assays. The compounds bind directly to FOXM1 and alter its proteolytic sensitivity, reduce the cellular level of FOXM1 protein, and suppress the proliferation of breast cancer cells. RNA-seq and gene set enrichment analyses indicate that the compounds NB-73 and NB-55 decrease the expression of FOXM1-regulated genes and suppress gene ontology processes known to be under FOXM1 regulation. Several compounds with favorable pharmacokinetic properties were studied in preclinical breast tumor models. One compound (NB-55) had good oral efficacy in suppressing the growth of FOXM1-containing breast tumors in NOD-SCID-gamma (NSG) mice, and several others (NB-73, NB-115, and NB-63) had good efficacy in tumor growth suppression by subcutaneous administration. Our findings identify and characterize a new class of compounds that effectively antagonize FOXM1 actions and tumor growth that may be suitable for further clinical evaluation in targeting aggressive breast cancers driven by FOXM1.
Overall design Examine the effects of various FOXM1 inhibitors on gene expression in both estrogen receptor positive and triple negative breast cancer cell lines.
Contributor(s) Ziegler YS, Laws MJ, Sanabria Guillen V, Kim SH, Smith BP, Gong P, Bindman N, Zhao Y, Carlson K, Yasuda MA, Singh D, Li Z, El-Ashry D, Madak-Erdogan Z, Katzenellenbogen JA, Katzenellenbogen BS
Citation(s) 31815181
Submission date Jun 06, 2019
Last update date Mar 10, 2020
Contact name Zeynep Madak-Erdogan
Phone 2173009063
Organization name University of Illinois at Urbana-Illinois
Department Food Science and Human Nutrition
Street address 1201 W. Gregory Dr, 359 ERML Hall
City Urbana
State/province Illinois
ZIP/Postal code 61801
Country USA
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (24)
GSM3860375 VEH.1: 9hr Vehicle; MCF-7 cells
GSM3860376 VEH.2: 9hr Vehicle; MCF-7 cells
GSM3860377 VEH.3: 9hr Vehicle; MCF-7 cells
BioProject PRJNA547636
SRA SRP200698

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE132343_DEG_9hrMCF7.csv.gz 1.2 Mb (ftp)(http) CSV
GSE132343_DEG_list231.csv.gz 820.0 Kb (ftp)(http) CSV
GSE132343_DEG_list_24hr_MCF7.csv.gz 854.7 Kb (ftp)(http) CSV
GSE132343_fpkm_231.csv.gz 498.5 Kb (ftp)(http) CSV
GSE132343_fpkm_24hrMCF7.csv.gz 519.0 Kb (ftp)(http) CSV
GSE132343_fpkm_9hrMCF7.csv.gz 961.1 Kb (ftp)(http) CSV
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