Transcriptomics

Dataset Information

0

RB-loss determines selective resistance and novel vulnerabilities in breast cancer modelsRB loss


ABSTRACT: The retinoblastoma tumor suppressor (RB1) plays a critical role in coordinating multiple pathways that impact on tumor initiation, disease progression, and therapeutic responses. Here we interrogated the effect of CDK4/6 inhibitor in combination with mTOR inhibtor. Also, we interrogtaed the efffect of AURK and WEE1 inhibition in ER+ breast cacner models While the RB-pathway has been purported to exhibit multiple mutually exclusive events, only RB1 is mutually exclusive with multiple genetic events that deregulate CDK4/6 activity. Using an isogenic ER+ breast cancer model with targeted RB1 deletion, we identified gene expression features that link CDK4/6 activity and RB-dependency (CDK4/6-RB integrated signature). We also investigated the role of RB on apoptotic pathway. Single copy loss on chromosome 13q encompassing the RB1 locus is prevalent in many cancers, and is associated with reduced expression of multiple genes on 13q including RB1, and inversely related to the CDK4/6-RB integrated signature supporting a genetic cause/effect relationship. To probe the broader implications on tumor biology, we investigated genes that are positively and inversely correlated with the CDK4/6-RB integrated signature. This approach defined tumor-specific pathways that could represent new therapeutic vulnerabilities associated with RB-pathway activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182631 | GEO | 2021/08/31

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2020-03-02 | GSE145316 | GEO
2022-01-14 | GSE176402 | GEO
2022-01-14 | GSE176403 | GEO
2021-05-26 | GSE153123 | GEO
2017-09-14 | PXD007708 | Pride
2023-07-11 | GSE236499 | GEO
2023-07-11 | GSE236498 | GEO
2023-07-11 | GSE236497 | GEO
2023-07-11 | GSE236496 | GEO
2014-01-01 | E-GEOD-37601 | biostudies-arrayexpress