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Differential gene expression in capillary endothelial cells after inducing unfolded protein response with a protein N‐glycosylation inhibitor
Author(s) -
Baksi Krishna,
Banerjee Aditi,
Banerjee Dipak K
Publication year - 2012
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.26.1_supplement.794.4
Subject(s) - downregulation and upregulation , angiogenesis , tunicamycin , gene , microarray analysis techniques , biology , cancer research , microarray , gene expression , microbiology and biotechnology , unfolded protein response , genetics
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 observed cell cycle arrest in G1 and induction of apoptosis by ER stress‐mediated unfolded protein response following transcriptional and translational attenuation in tunicamycin treated capillary endothelial cells. The effect is irreversible under tumor microenvironment. cDNA microarray analysis identified 133 and 464 genes sharing only 10 genes in 3h and 32h tunicamycin treated cells, respectively. 72.2% and 77.6% of these are upregulated whereas 27.8% and 22.41% are down regulated. Among these 45 genes encode for transcription (75% and 20% of which are upregulated) whereas 15 genes encode for cell cycle (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 profile of a number of these genes. To our knowledge, it is the first detailed study assessing the significance of a genome‐wide expression profiling for a glycotherapeutic treating breast cancer. Supported by NIH/NCRR/RCMI G12‐RR03035 (KB) and Susan G. Komen for the Cure BCTR056206 (DKB) grants.