• BMB Reports
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• v.48 no.6
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• pp.342-347
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• 2015

The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.459-466
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• 2016

Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than $Lnk^{-/-}$ MSCs. An ex vivo adipogenic differentiation assay showed that $Lnk^{-/-}$ MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) and its adipogenic target genes (LPL and FABP4) significantly decreased in $Lnk^{-/-}$ MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the $IGF-1/Akt/PPAR-{\gamma}$ pathway.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.6
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• pp.784-793
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• 2004

Major objective was to evaluate three doses of bST (POSILAC(R)) injected into Holstein cows during the transition period and through 56 d of lactation for potential to improve DMI, BCS, BW, metabolites, hormones, IGF-I and milk production. Biweekly injections of bST (0, 5.1, 10.2, or 15.3 mg bST/d) began 28 d before expected parturition and continued through 56 d postpartum. Twenty-three of the 25 multiparous Holstein cows assigned randomly to four groups completed experiment (7, 5, 6 and 5 cows/group, respectively). The DMI, BW and BCS were recorded weekly throughout the prepartum and postpartum periods and blood samples were collected thrice weekly for analyses of ST, insulin, $T_{4}$, $T_{3}$, IGF-I, glucose and NEFA. Milk yields were recorded daily through 60 d postpartum and milk components measured once weekly. Mathematical model for data analyses for prepartum and postpartum periods included treatment, calving month, and the two-factor interaction. Cows injected with 10.2 and 15.3 mg bST prepartum had greater mean prepartum concentrations of ST and IGF-I. Prepartum injections of bST did not affect prepartum BW or BCS. On average, cows injected postpartum better maintained their BCS during first 60 d of lactation (3.15$\pm$0.06, 3.12$\pm$0.007, 3.20$\pm$0.006 and 3.58$\pm$0.009). Treatments did not affect mean prepartum DMI but cows injected with 15.3 mg bST/d had greatest DMI and greatest mean daily MY during the first 3 wk and tended to be greater during first 60 d of lactation. Cows injected with two highest bST doses (10.1 and 15.2 mg/d) had greater mean postpartum concentrations of ST and $T_{3}$, but IGF-I, $T_{4}$, glucose and NEFA did not differ across groups. No adverse effects of bST treatment were observed.