Transcriptomics,Multiomics

Dataset Information

37

DNA microarray analysis in H69 cells treated with either vehicle, PIK75 targeting p110-alpha, or TGX221 targeting p110-beta


ABSTRACT: Purpose: The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell proliferation and survival and is frequently altered and activated in neoplasia, including carcinomas of the lung. In this study we investigated the potential of targeting the catalytic class IA PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types. Experimental Design: The expression of PI3K isoforms in patient specimens was analyzed. The effects on SCLC cell survival and downstream signaling were determined following PI3K isoform inhibition by selective inhibitors or down-regulation by small interfering RNA. Results: Over-expression of the PI3K isoforms p110 -alpha and p110-alpha was shown by immunohistochemistry in primary SCLC tissue samples. Targeting the PI3K p110 -alpha with RNA interference (RNAi) or selective pharmacological inhibitors resulted in strongly affected cell proliferation of SCLC cells in vitro and in vivo, while targeting p110-alph was less effective. Inhibition of p110 -alpha also resulted in increased apoptosis and autophagy, which was accompanied by decreased phosphorylation of Akt and components of the mammalian target of rapamycin (mTOR) pathway, such as the ribosomal S6 protein, and the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). A DNA microarray analysis revealed that p110-alpha inhibition profoundly affected the balance of pro- and anti-apoptotic Bcl-2 family proteins. Finally, p110 -alpha inhibition led to impaired SCLC tumor formation and vascularization in vivo. Conclusion: Together our data demonstrate the key involvement of the PI3K isoform p110 -alpha in multiple tumor-promoting processes in SCLC. 3 control samples, 3 samples for two treaments

REANALYSED by: E-GEOD-40564

ORGANISM(S): Homo sapiens  

SUBMITTER: Alexandre Arcaro  Hubert Rehrauer   Anna Wojtalla    

PROVIDER: E-GEOD-40564 | ArrayExpress | 2015-08-19

SECONDARY ACCESSION(S): GSE40564PRJNA174312

REPOSITORIES: GEO, ArrayExpress

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Publications

Targeting the phosphoinositide 3-kinase p110-α isoform impairs cell proliferation, survival, and tumor growth in small cell lung cancer.

Wojtalla Anna A   Fischer Barbara B   Kotelevets Nataliya N   Mauri Francesco A FA   Sobek Jens J   Rehrauer Hubert H   Wotzkow Carlos C   Tschan Mario P MP   Seckl Michael J MJ   Zangemeister-Wittke Uwe U   Arcaro Alexandre A  

Clinical cancer research : an official journal of the American Association for Cancer Research 20121121 1


The phosphoinositide 3-kinase (PI3K) pathway is fundamental for cell proliferation and survival and is frequently altered and activated in neoplasia, including carcinomas of the lung. In this study, we investigated the potential of targeting the catalytic class I(A) PI3K isoforms in small cell lung cancer (SCLC), which is the most aggressive of all lung cancer types.The expression of PI3K isoforms in patient specimens was analyzed. The effects on SCLC cell survival and downstream signaling were  ...[more]

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