Differential Regulation of ErbB2 Expression by cAMP-Dependent Protein Kinase in Tamoxifen-Resistant Breast Cancer Cells

Jin Won Yang,Hyung Gyoon Kim,Mi Ra Kim,김상겸,정혜광,강건욱 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.3

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients, and Her-2/ErbB2 expression is associated with decreased sensitivity to TAM. We previously reported that cAMP-dependent protein kinase (PKA)-mediated activator protein-2 (AP- 2) activation was responsible for the expression of Her-2/ErbB2 in p53-inactivated mammary epithelial cells (Yang et al., 2006). In the present study, we tested the hypothesis that PKA plays a role in the expression of ErbB2 in tamoxifen-resistant breast cancer cells. Treatment with H-89, a specific PKA inhibitor, suppressed 4-hydroxytamoxifen-induced ErbB2 expression in control MCF-7 cells. In contrast, PKA inhibition by H-89 or cAMP-dependent protein kinase inhibitor Iγ overexpression increased the expression levels of ErbB2 in TAM-resistant MCF-7 (TAMR-MCF-7) cells. Transcriptional regulation of the erbB2 gene depends on two transcription factors, AP-2 and polyomavirus enhancer activator3 (PEA3). H-89 decreased nuclear or total levels of PEA3 in TAMR-MCF-7 cells. Chromatin immunoprecipitation assay results revealed that H-89 treatment reduced PEA3 binding to the proximal Ets binding site of the erbB2 gene promoter. Reporter gene analyses using human erbB2 gene promoter supported the critical role of PEA3 in the overexpression of ErbB2 in TAMR-MCF-7 cells treated with H-89. This deregulated PKA signaling cascades required for the ErbB2 expression may be important for the differential response of TAM-resistant breast cancer cells to EGF/ErbB2 stimuli.

동영상 UCC의 선택과 이용의도의 영향 요인에 관한 연구

김은미(Eun Mi Kim),권상희(Sang Hee Kweon) 사이버커뮤니케이션학회 2010 사이버 커뮤니케이션 학보 Vol.27 No.2

본 연구는 동영상 UCC이용과 채택에 미치는 주요 요인을 측정한 논문이다. 이를 위해 이론적 배경으로 TAM2 모델을 적용하여 측정하였다. 동영상 형태의 UCC(User Created Contents)는 개방된 공간인 네트워크상에 올려놓는 기본적인 UCC의 특징과 함께 동영상의 형태를 가지고 있어서 이용자들이 인터넷상에서 자발적으로 참여하여 자신을 노출시키는 표현의 장으로 자리 잡고 있다. 이에 본 연구는 활발히 이용되고 있는 동영상 UCC의 선택과 지속적인 이용의도에 영향을 미치는 요인을 정보기술수용모형(Technology Acceptance Model: TAM)을 바탕으로 설명을 시도하였다. 본 연구를 위하여 설문 조사 방법을 실시하였으며 총 434명의 응답자의 자료를 연구가설을 측정하기위해 사용하였다. 본 연구 결과 이용자는 동영상 UCC를 선택하고 이용함에 있어서 기존에 생각하고 있던 이미지와 1) 기능적인 유사성 그리고 얼마나 2) 친숙하고 습관적으로 이용했었는지의 경험에 따라서 동영상 UCC를 사용하게 될 때, 용이하게 인식하고 지속적으로 동영상 UCC를 선택?이용하게 된다고 할 수 있다. 그리고 개인이 느끼는 동영상 UCC의 1) 필요성 2) 혁신성 3) 기능의 다양성 4) 대체성 등은 동영상 UCC를 유용하게 인식하게 하여 지속적으로 영향을 미치는 주요 변인으로 나타났다. This paper explores the adopting and usage of moving imaged UCC(User Created Contents) with applying the TAM model. As is the same level, this research is designed to explain the choice of actively used moving image UCC and to figure out the factors which affect the intention of constant use on the basis of Technology Acceptance Model(TAM, TAM2). The research measures the acceptance variables using constructed survey questionnaires, and 434 data was used to test TAM model. The results show that users easily recognizes and continuously selects, and uses moving image UCC when using moving image UCC, depending on their former image about moving image UCC, 1)the functional similarity and 2)experience of familiar and habitual use. 1)The necessity and 2)innovation of moving image UCC, 3)diversity of function, 4)substitute felt by individual in using moving image UCC affect the utility that recognizes the improvement of his or her work result. It was found that this affects the intention of constantly using moving image UCC.

Luteolin inhibits recruitment of monocytes and migration of Lewis lung carcinoma cells by suppressing chemokine (C–C motif) ligand 2 expression in tumor-associated macrophage

Choi, Hee-Jin,Choi, Hee-Jung,Chung, Tae-Wook,Ha, Ki-Tae Academic Press 2016 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>Tumor-associated macrophages (TAMs) play pivotal roles in the progression of cancer. In order to investigate a novel candidate that inhibits the tumor-supporting M2-like phenotype of TAMs, a murine macrophage cell line RAW 264.7 cells were treated with interleukin (IL)-4. Luteolin inhibited phosphorylation of signal transducer and activator of transcription 6 (STAT6), a main downstream signal of IL-4, and reduced the expression of the M2-associated genes. In addition, Luminex multiplex analysis for secreted cytokines revealed that IL-4–enhanced secretion of chemokine (C–C motif) ligand 2 (CCL2) was reduced by luteolin treatment. IL-4–stimulated migration of monocyte, THP-1 cells, was inhibited by luteolin treatment and recovered by recombinant CCL2 supplement. Moreover, luteolin decreased migration of Lewis lung carcinoma cells in a CCL2–dependent manner. Given the important role of the TAM phenotype in the tumor microenvironment, inhibitory effect of luteolin on the monocyte recruitment and cancer migration via suppression of the TAM-secreted CCL2 may suggest a novel therapeutic approach to treat malignant tumors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> M2-polarized TAMs play pivotal roles in the progression of cancer. </LI> <LI> IL-4 shift macrophages to M2 polarization through STAT6 activation. </LI> <LI> Luteolin inhibited STAT6 activation and CCL2 secretion. </LI> <LI> Migration of monocytes and cancer cells was reduced by luteolin. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

자동차 O2O 서비스의 특성에 따른 소비자 수용의도변화 분석

김누리,이대호 한국혁신학회 2016 한국혁신학회지 Vol.11 No.1

The automobile industry, which has traditionally advanced with much of its focus on hardware, recently began to integrate with ICT and became a new growth sector with respect to software and service. In particular, the emergence of “Uber” induced a long line of automobile-related O2O services, mainly on-demand O2O services. However, it’s still an early stage for these new services, only few previous studies on the automobile-related O2O services are available. In this study, focusing on various automobile-related O2O services, the personal contact between consumers and service providers occurring during the use of services was taken as a critical factor in O2O service business. The services were categorized into the three groups, “Zero step”, “One step”, and “Two step” according to the presence and type of the personal contact. A survey on O2O services were carried out, and, based on the survey responses, the consumer acceptance of automobile- related O2O services in each group were analyzed using technology acceptance model (TAM). In the results, all relationships except between perceived performance risk, perceived safety and intention to use were not confirmed. The reasons why the two characteristics are not confirmed are as follows; the one might be of the offline feature of O2O services and the other would be positive change of consumer’s attitude to common mobile services. Based 전통적으로 하드웨어를 중심으로 발전해온 자동차 산업이 최근 ICT와 융합되면서 소프트웨어 혹은 서비스 측면에서 혁신적인 신 성장 분야로 발전하고 있다. 특히 ‘우버’의 등장으로 인해 온디맨드형 O2O 서비스를 주축으로 자동차 관련 O2O 서비스들이 줄을 잇고 있다. 그러나 아직 신규 서비스 도입시기이기 때문에 자동차 O2O 서비스 관련 선행연구는 많이부족한 상태이다. 이에 본 연구는 다양한 자동차 O2O 서비스들을 중심으로 소비자가 서비스를 사용하는 과정 중 발생하는 자동차 O2O 서비스 제공 주최자와의 개인적 만남(Personal contact)을 주요한 이슈로 판단하였다. 이를 기준으로 ‘Zero step’, ‘One step’, ‘Two step’ 세가지로 서비스를 분류하여 확장된 기술수용모델(TAM2)을 기반으로 설문을 통해 각 그룹별로 자동차 O2O 서비스 수용의도의 차이를 분석하였다. 분석 결과 ‘지각된 수행 위험’, ‘지각된 안정성’과 수용의도 간의 가설을 제외하고는 모두지지되었다. 위의 요인들이 유의한 영향을 미치지 못한 이유로 O2O의 오프라인 특성과 소비자들의 보편화된 모바일 서비스에 대한 긍정적인 태도 변화 때문인 것으로 해석되었다.

Enhancement of antitumor effect of radiotherapy via combination with Au@SiO2 nanoparticles targeted to tumor-associated macrophages

Mi Sun Kim,Jae Sang Lee,Jung-Eun Kim,Jae-Won Kim,복서연,KiChangKeum,Won-Gun Koh,Woong Sub Koom 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.84 No.-

Tumor-associated macrophages (TAMs) exhibit the M2 phenotype and serve as critical tumor-promotingimmune cells in the tumor microenvironment. As TAMs are an important target, we examined the effectof gold nanoparticles (AuNPs) with radiotherapy (RT) on M2 TAMs in tumors. We synthesized CD163antibody-conjugated, silica-coated AuNPs (CD163-GNPs) that were specifically recognized by M2 TAMs. Bone marrow-derived macrophages and Raw 264.7 macrophages were polarized into M1 and M2phenotypes. The effect of CD163-GNPs combined with RT was evaluated in a CT26 syngeneic mousemodel (BALB/c mice). Immunostaining,flow cytometry, microscopic analyses, enzyme-linkedimmunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), and tumor growthdelay assay were performed following irradiation combined with CD163-GNP treatment. We observedselective phagocytosis of CD163-GNPs by Raw 264.7 macrophages following M1/M2 polarization. Immunostaining analyses revealed higher numbers of CD163-GNPs taken up by M2 macrophages thanM0 or M1 type. CD163-GNPs combined with RT significantly reduced tumor growth in the CT26syngeneic mouse model. Macrophages subjected to the combination treatment showed increasedexpression of M1 markers. The depletion of M2 TAMs in tumors upon combination treatment withCD163-GNPs enhances the efficiency of RT.

Tumor-associated macrophages secrete CCL2 and induce the invasive phenotype of human breast epithelial cells through upregulation of ERO1-α and MMP-9

Lee, Seungeun,Lee, Eunhye,Ko, EunYi,Ham, Mina,Lee, Hye Min,Kim, Eun-Sook,Koh, Minsoo,Lim, Hyun Kyung,Jung, Joohee,Park, So Yeon,Moon, Aree Elsevier 2018 Cancer letters Vol.437 No.-

<P><B>Abstract</B></P> <P>Tumor-associated macrophages (TAMs) are major components of tumor microenvironment that promote invasion and metastasis of cancer cells. In this study, we investigated the effect of TAMs on phenotypic conversion of non-neoplastic MCF10A human breast epithelial cells using an indirect co-culture system. Co-culture with TAMs induced epithelial-to-mesenchymal transition, invasive phenotype, and MMP-9 upregulation in MCF10A cells. Comparative proteomic analysis revealed that endoplasmic reticulum oxidoreductase (ERO)1-α was increased in MCF10A cells co-cultured with TAMs compared to that in mono-cultured cells. ERO1-α was crucial for TAMs-induced invasive phenotype and MMP-9 upregulation involving transcription factors c-fos and c-Jun. Cytokine array analysis showed that levels of interleukin (IL)-6, C-X-C motif ligand (CXCL)1, C-C motif ligand (CCL)2, growth-regulated protein (GRO), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in conditioned media of co-cultured cells. Among these cytokines increased in conditioned media of co-cultured cells, CCL2 was secreted from TAMs, leading to induction of ERO1-α, MMP-9 upregulation, and invasiveness in MCF10A cells. Our findings elucidated a molecular mechanism underlying the aggressive phenotypic change of non-neoplastic breast cells by co-culture with TAMs, providing useful information for prevention or treatment of recurrent breast cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TAMs induced invasion in MCF10A cells non-neoplastic human breast epithelial cells. </LI> <LI> ERO1-α was increased in MCF10A cells co-cultured with TAM. </LI> <LI> ERO1-α was crucial for the TAMs-induced invasive phenotype and MMP-9 upregulation. </LI> <LI> CCL2 was secreted from TAMs co-cultured with MCF10A cells. </LI> <LI> CCL2 induced ERO1-α, resulting MMP-9 upregulation and invasiveness in MCF10A cells. </LI> </UL> </P>

An Empirical Study on Technology Acceptance for e-Commerce in Developing Countries

Gilbert M. Tumibay,Chong-Su Kim,Hyun-Seung Oh,Kyeongtaek Kim 한국산업경영시스템학회 2009 한국산업경영시스템학회 학술대회 Vol.2009 No.추계

As e-commerce such as online shopping continues to become a popular option, consumers are increasingly moving from traditional stores to online sites. However, the adoption of B2C e-commerce and related technologies so far has mostly been limited to developed countries. It has been relatively slower in the rest of the world. The acceptance for B2C e-commerce in developing countries is relatively not active. To understand this properly, a comprehensive model describing the factors that drive customers to accept B2C e-commerce is required. In this paper, a TAM-based theoretical model is proposed and tested to explain the information technology acceptance of B2C e-commerce in developing countries. The results show that the basic TAM beliefs are supported. PU and PEOU determine a person's attitude toward using B2C e-commerce, which in turn determines their intention to use it. The antecedents show a different form of influence from that of developed countries. The results of this work would be useful for both academic societies and online e-commerce practitioners, helping them to better comprehend customers' online shopping behavior.

Comparison of the Growth Inhibition by Alpha-Difluoromethylornithin and Hydroxytamoxifen in MCF-7 Human Breast Cancer Cells

Kim, Byeong-Gee,Seok, Sorah,Lee, Kyeong-Hee,Lee, Ji-Young,Park, Won-Hyuck Korean Society of Life Science 2001 Journal of Life Science Vol.11 No.1

In estrogen-dependent MCF-7 human breast cancer cells, $E_2$ at 10 nM stimulated cell proliferation to over 200% compared to the untreated control. EGF and TGF${\alpha}$, which are known as the autocrine/paracrine growth factors induced by $E_2$, also directly stimulated the cell growth in almost as the same extent as $E_2$. DFMO which is the specific inhibitor of ODC could inhibit cell growth even at as low as 0.5 mM. In the treatment with 1 mM DFMO for 4 days, the cell growth was inhibited to 38% of the control. HO-TAM at 1 ${\mu}$M could inhibit the proliferation of MCF-7 cells to 19% of the control. Those inhibitory effects were also found in the cells stimulated with $E_2$, EGF, and TGF${\alpha}$. The inhibitory effects were found even in 2 days of treatment. However, $E_2$, EGF, and TGF${\alpha}$ did not give any effect in the protein synthesis. Neither DFMO or HO-TAM gave any effect on the total protein synthesis. But the pattern of protein secretion was noticeably influenced by the growth stimulants or inhibitors. Proteins of 160, 52, 42, 36, and 32 kDa belonged to the major secretory proteins. Especially, 42 and 36 kDa proteins were most significantly influenced by the treatment of $E_2$, EGF, or TGF$\alpha$. DFMO and HO-TAM inhibited the secretion of these major proteins.

외식기업 O2O 서비스 품질이 지각된 유용성, 지각된용이성, 순편익 및 고객만족에 미치는 영향

반기,서진욱 사단법인 한국비즈니스이벤트컨벤션학회 2023 이벤트 컨벤션 연구 Vol.19 No.1

Purpose –This study attempted to propose a milestone in service quality management on how O2O service quality of food service companies should be provided to consumers in terms of technology acceptance under the rapid growth of non-face-to-face services due to the development of information and communication technology and the prolonged COVID -19 pandemic. Design, data, and methodology –In this study, we conducted a study on the quality of O2O service using SERVQUAL, TAM and UISSM. Empirical analysis was conducted using explor atory factor analysis, confirmatory factor analysis, reliability analysis, correlation analysis, and structural equation model based on the data of 420 questionnaires collected from servic e users with experience using O2O service. Result – As a result of verifying a total of 7 hypotheses and 16 sub-hypothesis, the study results showed that all hypothesis paths except for 2 sub-hypothesis had a significant influen ce relationship. Conclusions – Food service companies should constantly develop and implement strategic meas ures by maximizing customer satisfaction by improving reliability and accuracy through timely info rmation update of O2O service platform and providing convenience and simplicity of use.

노인요양시설 장기요양인력의 스마트 기술 사용의도에 대한 탐색적 분석

안준희(Joon Hee Ahn),이선형(Sun Hyung Yi) 한국노인복지학회 2015 노인복지연구 Vol.0 No.68

본 연구는 노인요양시설의 장기요양인력을 대상으로 스마트 기술 사용의도를 파악하고 이에 관련되어 있는 요인들과 그 관계양상을 밝히고자 하였다. 기술수용모델(TAM)을 사용하여, 스마트 기술에 대한 지각된 용이성, 지각된 유용성, 사용의도 사이의 구조적 관계를 밝히고자 하였다(연구모형 1). 또한 확장된 기술수용모델(TAM2)을 사용하여, 스마트 기술사용에 대한 주관적 규범, 직무 관련성, 지각된 유용성, 사용의도 사이의 구조적 관계를 밝히고자 하였다(연구모형 2). 조사대상자는 충청남도와 경기지역에 위치한 노인요양시설의 장기요양인력 127명이었으며, 설문지법을 이용하여 자료를 수집하였다. 연구결과로는 조사대상자 중72.4%가 스마트 기술에 대한 사용의도를 긍정적으로 평가했으며, 이러한 사용의도에 지각된 용이성과 유용성이 직접적인 유의미한 영향을 미치는 것으로 나타났다. 주관적 규범, 물리적환경 지원 및 건강지원 직무관련성은 사용의도 뿐 아니라 지각된 유용성에 직접적인 유의한 영향을 미치는 것으로 나타났다. 또한 지각된 유용성은 연구모형(1, 2)에서 부분매개효과가 있음이 밝혀졌다. 이러한 결과를 기반으로 노인요양시설에서 스마트 기술을 성공적으로 도입하기 위한 증거 기반적 전략을 제시하고 있다. The purpose of this study is to examine contributors to the usage intention of smart technology by care workers in long-term care facilities in Korea. Based on the technology acceptance model (TAM1), this study examined the structural relationships between perceived ease of use(PEU), perceived usefulness(PU), and usage intention(UI). Additionally, this study analyzed the structural relationships between external variables (subjective norm, job relevance), PU, and UI based on the extended technology acceptance model (TAM2). The data were collected from the cross-sectional survey of 127 care workers. Results showed that PEU and PU had significant positive effects on care workers’ employed at long-term care facilities. UI, with PU having partial mediating effects between PEU and UI. Subjective norm, physical support job relevance, health support job relevance had significant direct effects on both PU and UI. PU also had partial mediating effects between those three external variables (subjective norm, physical support job relevance, health support job relevance) and UI. Implications are discussed in that smart technology should be developed in ways to be usefulness and easy to use in order to be introduced into long-term care facilities. Efforts should be also focused on forming a positive social norm for the introduction of the smart device and developing smartifact application to assist services for physical adjustment as well as health support for the elderly in the facilities.