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Genome‐wide expression profiling in capillary endothelial cells following Tunicamycin‐induced unfolded protein response
Author(s) -
Banerjee Dipak K,
Banerjee Aditi,
Baksi Krishna
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.964.1
Subject(s) - downregulation and upregulation , tunicamycin , gene , angiogenesis , biology , cancer research , gene expression profiling , gene expression , microbiology and biotechnology , genetics , unfolded protein response
Angiogenesis is a hallmark of breast tumor growth and progression. Our objective has been to understand the dynamic relationship between asparagine‐linked (N‐linked) protein glycosylation and angiogenesis. We have used a protein N‐glycosylation inhibitor Tunicamycin and observed that it arrests cells in G1 and induces apoptosis by unfolded protein response mediated by transcriptional (ATF6) and translational (PERK) attenuation. The effect is stable under tumor microenvironment. Differential gene expression identified that out of 20,908 genes 133 and 464 genes are involved at 3h and 32h of Tunicamycin treatment sharing only 10 genes. 72.2% and 77.6% of these are upregulated whereas 27.8% and 22.41% are down regulated, respectively. 45 genes encode for transcription, 75% and 20% of which are upregulated whereas 15 genes encode cell cycle and 40% and 20% of which are upregulated at 3h and 32h, respectively. Only 10 genes encode for translation, 80% of which are upregulated at 32h. Interestingly, only one gene is upregulated at 32h for protein folding, DNA inhibition and angiogenesis. Real‐time PCR validated and confirmed the expression pattern of a number of these genes. To our knowledge, this first detailed study assessed the significance of genome‐wide expression profiling for glycotherapeutics treating breast cancer. Supported in part by Susan G. Komen for the Cure BCTR056206 (DKB) and NIH/NCRR/RCMI G12‐RR03035 (KB) grants..