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Lee, Daekee,Yu, Ming,Lee, Eunjung,Kim, Hyunok,Yang, Yanan,Kim, Kyoungmi,Pannicia, Christina,Kurie, Jonathan M.,Threadgill, David W. American Society for Clinical Investigation 2009 The Journal of clinical investigation Vol.119 No.9
<P>Pharmacologic blockade of EGFR or the closely related receptor ERBB2 has modest efficacy against colorectal cancers in the clinic. Although the upregulation of ERBB3, a pseudo-kinase member of the EGFR/ERBB family, is known to contribute to EGFR inhibitor resistance in other cancers, its functions in normal and malignant intestinal epithelium have not been defined. We have shown here that the intestinal epithelium of mice with intestine-specific genetic ablation of Erbb3 exhibits no cytological abnormalities but does exhibit loss of expression of ERBB4 and sensitivity to intestinal damage. By contrast, intestine-specific Erbb3 ablation resulted in almost complete absence of intestinal tumors in the ApcMin mouse model of colon cancer. Unlike nontransformed epithelium lacking ERBB3, intestinal tumors lacking ERBB3 had reduced PI3K/AKT signaling, which led to attenuation of tumorigenesis via a tumor-specific increase in caspase-3-mediated apoptosis. Consistent with the mouse data, which suggest that ERBB3-ERBB4 heterodimers contribute to colon cancer survival, experimentally induced loss of ERBB3 in a KRAS mutant human colon cancer cell line was associated with loss of ERBB4 expression, and siRNA knockdown of either ERBB3 or ERBB4 resulted in elevated levels of apoptosis. These results indicate that the ERBB3 pseudo-kinase has essential roles in supporting intestinal tumorigenesis and suggest that ERBB3 may be a promising target for the treatment of colorectal cancers.</P>
Kwon, Daekee,Kang, Gwang-Sik,Han, Dong Keun,Park, Kwideok,Kim, Jae-Hwan,Lee, Soo-Hong 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.1
Commercially available extracellular matrix (ECM) hydrogel-coated culture plates have been used to study the relationship between the ECM microenvironment and stem cell behavior. However, it is unclear whether ECM-coated dishes mimic the natural ECM microenvironment because the architecture of the ECM is constructed of randomly distributed fibers. The purpose of this study was the production and confirmation of human engineered cell lines stably expressing large ECM proteins such as collagen I/II and fibronectin. First, large (over 10 kb) ECM vectors encoding human collagen I/II and fibronectin were constructed and the circular vectors were linearized. Second, the linear ECM vectors were introduced into immortalized human embryonic kidney cells using various transfection methods. The polyethylenimine and liposome methods showed higher efficiencies than electroporation for transfection of these large vectors. Third, human ECM engineered cells were established by stable integration of the vector into the genomic DNA and resulted in stable overexpression of mRNA and proteins. In summary, human engineered cell lines stably expressing large ECM proteins such as human collagen I/II and fibronectin were successfully prepared, and secretion of the ECM components into the surrounding environment was confirmed by immunocytochemistry. Thus, human ECM engineered cells naturally secreting ECM components could be valuable for studying the relationship between the native ECM microenvironment and stem cell behavior.
Nahm, Minyeop,Kim, Sungdae,Paik, Sang Kyoo,Lee, Mihye,Lee, Seongsoo,Lee, Zang Hee,Kim, Jaesang,Lee, Daekee,Bae, Yong Chul,Lee, Seungbok The Society 2010 The Journal of neuroscience Vol.30 No.24
<P>The bone morphogenetic protein (BMP) ligand Glass bottom boat (Gbb) acts as a retrograde growth signal at the Drosophila neuromuscular junction (NMJ). Endocytic regulation of presynaptic BMP receptors has been proposed to attenuate retrograde BMP signaling. However, it remains unknown whether the Gbb signal is also regulated by postsynaptic mechanisms. Here, we provide evidence that Drosophila Cdc42-interacting protein 4 (dCIP4) functions postsynaptically to inhibit synaptic growth. dCIP4 is localized postsynaptically at NMJs. dcip4 mutations lead to synaptic overgrowth and increased presynaptic phosphorylated mothers against decapentaplegic (Mad) levels, and these defects are rescued by muscle-specific expression of dCIP4. Biochemical and genetic analyses demonstrate that dCIP4 acts downstream of Cdc42 to activate the postsynaptic Wsp-Arp2/3 pathway. We also show that BMP signaling is necessary for synaptic overgrowth in larvae lacking postsynaptic dcip4 or wsp. Finally, dCIP4 and Wsp inhibit Gbb secretion. Thus, we propose that dCIP4 restrains synaptic growth by inhibiting postsynaptic Gbb secretion through the Wsp-Arp2/3 pathway.</P>
Isolation and Functional Examination of the Long Non-Coding RNA Redrum
Lee, Yerim,Park, Charny,Lee, Sanghyuk,Lee, Daekee,Kim, Jaesang Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.2
Here, we report isolation of multiple long non-coding RNAs (lncRNAs) expressed tissue-specifically during murine embryogenesis. One of these, subsequently came to be known as Redrum, is expressed in erythropoietic cells in fetal liver and adult bone marrow. Redrum transcription is also detected during pregnancy in the spleen where extramedullary hematopoiesis takes place. In order to examine the function of Redrum in vivo, we generated a gene-targeted murine model and analyzed its embryonic and adult erythropoiesis. The homozygous mutant embryo showed no apparent deficiency or defect in erythropoiesis. Adult erythropoiesis in bone marrow and in the spleen during pregnancy likewise showed no detectable phenotype as red blood cells matured in normal fashion. The phenotype is in contrast to the reported function of Redrum in vitro, and our observation implies that Redrum plays in vivo an accessory or supplementary role whose loss is compatible with normal erythropoiesis.