N-Acetylglucosaminyl 1-Phosphate Transferase: An Excellent Target for Developing New Generation Breast Cancer Therapeutic
| Autor: | Dipak K. Banerjee, Juan A. Martinez, Jesus Santiago, Aditi Banerjee, Krishna Baksi, Zhenbo Zhang, Maria O. Longas |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Time Factors Angiogenesis Cell Mice Nude Transferases (Other Substituted Phosphate Groups) Breast Neoplasms DNA Fragmentation Biology Spectrum Analysis Raman Article Cell Line chemistry.chemical_compound In vivo Cell Line Tumor Internal medicine medicine Animals Humans Phosphorylation Cell Proliferation Tumor microenvironment Vascular Endothelial Growth Factor Receptor-1 Dose-Response Relationship Drug Neovascularization Pathologic Cell growth Tunicamycin Endoplasmic Reticulum Stress Vascular Endothelial Growth Factor Receptor-2 Xenograft Model Antitumor Assays Tumor Burden Endocrinology medicine.anatomical_structure chemistry Apoptosis Unfolded protein response Cancer research Female |
| Zdroj: | Advances in Experimental Medicine and Biology ISBN: 9783319112794 |
| DOI: | 10.1007/978-3-319-11280-0_22 |
| Popis: | Studies from our laboratory have explained that breast tumor progression can be attenuated by targeting the N-linked glycoproteins of the tumor microvasculature and that of tumor cells alike with a protein N-glycosylation inhibitor, tunicamycin. Absence of N-glycosylation leads to an accumulation of un- or mis-folded proteins in the ER and the cell develops “ER stress”. The result is cell cycle arrest, and induction of apoptosis mediated by unfolded protein response (upr) signaling. Tunicamycin inhibited in vitro and in vivo (Matrigel™ implants in athymic nude mice) angiogenesis in a dose dependent manner. The action is irreversible and survived under tumor microenvironment, i.e., in the presence of FGF-2 or VEGF or higher serum concentration. Importantly, tunicamycin prevented the progression of double negative (ER-/PR-/Her2+) and triple negative (ER-/PR-/Her2-) breast tumors by ∼55% - 65% in three weeks in athymic nude mice [Balb/c(nu/nu)]. Analyses of paraffin sections exhibited “ER stress” in both microvasculature and in tumor tissue. |
| Databáze: | OpenAIRE |
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