github link
Accession IconSRP092159

Analysis of gene expression (RNAseq) from shTP53:RB1 LNCaP/AR cell lines

Organism Icon Homo sapiens
Sample Icon 11 Downloadable Samples
Technology Badge IconIllumina HiSeq 2500

Submitter Supplied Information

Description
Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. Here we show, using in vitro and in vivo prostate cancer models, that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR) dependent luminal epithelial cells to AR independent basal-like cells. This lineage plasticity is enabled by loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2 and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression. Thus, mutations in tumor suppressor genes can create a state of increased cellular plasticity that, when challenged with antiandrogen therapy, promotes resistance through lineage switching. Overall design: LNCaP/AR prostate cell line was transduced with shNT or shTP53:RB1 hairpins and then RNA was harvested from these cell lines for gene epxression analysis.
PubMed ID
Total Samples
11
Submitter’s Institution
No associated institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Cell line
Subject
Processing Information
Additional Metadata
No rows found
Loading...