Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Oncogenic PI3K mutations lead to NF-kB-dependent cytokine expression following growth      
keywords:
Transcriptome or Gene expression
ID:
PRJNA162691
description:
While growth factor-independent signaling and proliferation are well-established hallmarks of cancer, little is known regarding growth factor-independent changes in gene expression which occur downstream from oncogenes. The PI3K pathway is one of the most commonly misregulated signaling pathways in human cancers. Here, MCF10A cells expressing the two most common PI3K mutations, PIK3CA E545K and H1047R, were used to identify the repertoire of genes altered by oncogenic PI3K mutations following growth factor deprivation. This gene set most closely correlated with gene signatures from claudin-low and basal-like breast tumors, and categorical enrichment analyses suggested that NF-kB target genes were dramatically upregulated by these mutations. An IKKb inhibitor was used to identify the subset of PI3K-driven genes that is NF-kB dependent. Interestingly, virtually all of these NF-kB dependent genes were secreted proteins, suggesting a paracrine role for this gene set. Among these genes was IL-6, a cytokine frequently expressed in tumors which plays a critical role in generating a tumor-promoting microenvironment. Consistent with this, conditioned media from cells expressing the E545K or H1047R mutations led to increased STAT3 activation in recipient THP-1 monocytes or normal epithelial cells in a NF-kB and IL-6-dependent manner. Together, these data describe a PI3K-driven, NF-kB-dependent gene expression profile which may play a critical role in promoting a microenvironment amenable to tumor progression. Overall design: 39 normal cell lines vs treated cell lines for micorarray analysis
accesstypes:
download
landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA162691
authentication:
none
authorization:
none
ID:
pmid:22552288
dateReleased:
05-01-2012
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R37 AI035098/AI/NIAID NIH HHS/United States

  • R01 CA075080/CA/NCI NIH HHS/United States

  • R01 CA138255/CA/NCI NIH HHS/United States

  • CA73756/CA/NCI NIH HHS/United States

  • R01 CA148761/CA/NCI NIH HHS/United States

  • P50 CA058223/CA/NCI NIH HHS/United States

  • R01 CA138937/CA/NCI NIH HHS/United States

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.