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Series GSE117743 Query DataSets for GSE117743
Status Public on Mar 04, 2019
Title MicroRNA-mediated suppression of the TGF-β pathway confers transmissible and reversible CDK4/6 inhibitor resistance (array II)
Organism Homo sapiens
Experiment type Expression 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. In this experiment we extracted RNA from parental, resistant and Ex-resistant (resistant cells after prolonged drug removal) cells. We used the affymetrix Human Genome U133+ 2.0 array to analyse gene expression
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)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (9)
GSM3308126 Parental cell RNA dataset 2 repeat 1
GSM3308127 Parental cell RNA dataset 2 repeat 2
GSM3308128 Parental cell RNA dataset 2 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 PRJNA483060

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Supplementary file Size Download File type/resource
GSE117743_RAW.tar 17.5 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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