GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE117745 Query DataSets for GSE117745
Status Public on Mar 04, 2019
Title MicroRNA-mediated suppression of the TGF-ß pathway confers transmissible and reversible CDK4/6 inhibitor resistance (miRNA array)
Platform organisms Homo sapiens; Human alphaherpesvirus 1; Human alphaherpesvirus 2; Cytomegalovirus; Lymphocryptovirus; Rhadinovirus; JC polyomavirus; Human immunodeficiency virus 1; Merkel cell polyomavirus; Betapolyomavirus hominis; Betapolyomavirus macacae
Sample organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday.
Overall design T47D cells were cultured to palbociclib resistance. We extracted RNA from parental, resistant, and parental T47D cells cultured in resistant cell media and analysed the expression of 3100 miRNAs using the Exiqon 7th generation miRCURY LNATM microRNA
Contributor(s) Cornell L, Shapiro GI
Citation(s) 30840889
Submission date Jul 26, 2018
Last update date Apr 17, 2019
Contact name Liam Cornell
Organization name Dana-Farber Cancer Institute
Street address 450 brookline avenue
City boston
State/province MASSACHUSETTS
ZIP/Postal code 02215
Country USA
Platforms (1)
GPL19128 Exiqon miRCURY LNA microRNA array; 7th generation - hsa, mmu & rno (miRBase 18.0)
Samples (9)
GSM3308139 Parental cell RNA repeat 1
GSM3308140 Parental cell RNA repeat 2
GSM3308141 Parental cell RNA repeat 3
This SubSeries is part of SuperSeries:
GSE117748 MicroRNA-mediated suppression of the TGF-β pathway confers transmissible and reversible CDK4/6 inhibitor resistance
BioProject PRJNA483059

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

Supplementary file Size Download File type/resource
GSE117745_RAW.tar 25.1 Mb (http)(custom) TAR (of TXT)
GSE117745_normalized.txt.gz 113.5 Kb (ftp)(http) TXT
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap