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Series GSE149205 Query DataSets for GSE149205
Status Public on Jul 31, 2020
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Non-small cell lung cancer (NSCLC), the most frequent subtype of lung cancer, remains a highly lethal malignancy and one of the leading causes of cancer deaths worldwide. Mutant KRAS is the prevailing oncogenic driver of lung adenocarcinoma, the most common histological form of NSCLC. In this study, we examined the role of PKCe, an oncogenic kinase highly expressed in NSCLC and other cancers, in KRAS-driven tumorigenesis. Notably, database analysis revealed an association between PKCe expression and poor outcome in lung adenocarcinoma patients specifically having KRAS mutation. By generating a PKCe-deficient, conditionally activatable allele of oncogenic Kras (LSL-Kras G12D ;PKCe -/- mice) we were able to demonstrate the requirement of PKCe for Kras-driven lung tumorigenesis in vivo, which is consistent with the impaired transformed growth observed in PKCe-deficient KRAS-dependent NSCLC cells. Moreover, PKCe-knockout mice were found to be less susceptible to lung tumorigenesis induced by benzo[a]pyrene, a carcinogen that induces mutations in Kras. Mechanistic analysis using RNA-Seq revealed little overlapping for PKCe and KRAS in the control of genes/biological pathways relevant in NSCLC, suggesting that a permissive role of PKCe in KRAS-driven lung tumorigenesis may involve non-redundant mechanisms. Our results thus highlight the relevance and potential of targeting PKCe for lung cancer therapeutics.
Overall design H2009 cells were subjected to PKCe RNAi (e1 or e3 duplexes) or KRAS RNAi (K1 or K3 duplexes). As controls we used NTC RNAi and parental cells. Three replicates were done for each condition. Forty-eight h later, total RNA was isolated from subconfluent plates.
Contributor(s) Kazanietz MG, Abba MC
Citation(s) 32994205
Submission date Apr 23, 2020
Last update date Oct 30, 2020
Contact name Martin Carlos Abba
Phone 054-221-4236711
Organization name School of Medical Sciences - UNLP
Street address 60 y 120
City La Plata
State/province Buenos Aires
ZIP/Postal code 1900
Country Argentina
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (18)
GSM4492214 NTC_1_AB
GSM4492215 NTC_2_AB
GSM4492216 NTC_3_AB
BioProject PRJNA627658
SRA SRP258099

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

Supplementary file Size Download File type/resource
GSE149205_Processed_datamatrix.csv.gz 1.8 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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