Pregnancy-associated plasma protein-A (PAPP-A) is known as an important biomarker for fetal abnormality during first trimester and has a pivotal role in follicle development and corpus luteum formation. And also, it is being revealed that an expression of PAPP-A in various cells and tissues such as cancer and lesion area. PAPP-A is the major IGF binding protein-4 (IGFBP-4) protease. Cleavage of IGFBP-4 results in loss of binding affinity for IGF, causing increased IGF bioavailability for proliferation, survival, and migration. Additionally, PAPP-A can be used as a promising therapeutic target for healthy longevity. Despite growing interest, almost nothing is known about how PAPP-A expression is regulated in any tissue. This review will focus on what is currently known about the zinc metalloproteinase, PAPP-A, and its role in cells and tissues. PAPP-A is expressed in proliferating cells such as fetus in uterus, granulosa cells in follicle, dermis in wound, cancer cells, and Sertoli cells in testis. They have common characteristics of proliferation faster than normal cells with stimulating IGFs action and inhibiting IGFBPs. The PAPP-A functions and expression studies in livestock have not yet been conducted much. Further studies are needed to use PAPP-A as a marker for healthy longevity in animal science.
Diabetic nephropathy is associated with the dysfunction of proximal tubule cells. Insulin-like growth factor 1(IGF-I) has also been considered to play an important role in the development of diabetic nephropathy. Ginsenosides have been used as a remedy for diabetes in Asian countries. Therefore, we examined the preventive effect of ginsenosides against high glucose-induced alteration of IGF-I secretion in the primary cultured proximal tubule cells. In present study, Ginseng saponin (GS) completely blocked high glucose-induced stimulation of IGF-I secretion in proximal tubule cells, whereas panaxatriol (PI) and panaxadiol (PD) partially suppressed. In addition, high glucose stimulated cAMP formation and protein kinase C(PKC) activity from cytosolic to membrane fraction. GS completely prevented high glucose-induced stimulation of cAMP and PKC activity while PT and PD partially did. Furthermore, high glucose-induced stimulation of IGF-I was blocked by the treatment of PKI (protein kinase A inhibitor) and bisindolylmaleimide I (protein kinase C inhibitor). In conclusion, GS prevented high glucose-induced dysfunction of proximal tubule cells.
Journal of the Korean Society of Food Science and Nutrition
/
v.32
no.3
/
pp.437-443
/
2003
Epidemiological data suggest that lycopene has anticancer activities in humans. Insulin-like growth factor-I receptor (IGF-IR) is a transmembrane tyrosine kinase that mediates the biological actions of IGFs and may play an active role in cancer progression. Because our previous in vitro studies have indicated lycopene inhibits HT-29 cell growth, the aim of this study was to determine whether lycopene induces apoptotic cell death and the inhibitory effect of lycopene on HT-29 cell growth is related to changes in IGF-IR levels and the receptor's intracellular signalling pathways. HT-29 cells were incubated for 4 days in serum-free medium in the presence of 0, 25, 50, or 100 $\mu$M lycopene, and the DNA fragmentation assay was performed. Cells treated with lycopene produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. HT-29 cells were cultured for 4 days in serum-free medium in the presence of 0~100 $\mu$M lycopene and IGF-I (10nM) was added for 0~60 minutes immediately prior to lysate preparations. Western blot analysis of total lysates revealed that lycopene decreased the levels of IRS-1, Akt, phosphatidylinositol 3-kinase (PI3K), and IGF-IR $\beta$-subunit, and increased the levels of the IGF-IR precursor dose dependently. Lycopene also decreased IGF-I-induced phosphorylation of IGF-IR$\beta$, IRS-1 and Akt, which were, at least in part, due to decreased expression of these proteins. These results suggest that lycopene induces apoptosis of HT-29 cells by inhibiting IGF-IR signaling thereby interfering with an IGF-II-driven autocrine growth loop, which is known to exist in this cell line.
Park, Ji-Hyun;Kang, Myoung-Jae;Lee, Heung-Bum;Lee, Yong-Chul;Rhee, Yang-Kuen
Tuberculosis and Respiratory Diseases
/
v.48
no.3
/
pp.324-330
/
2000
Objective : Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. Multiple molecular changes and growth factor production have been documented in lung cancers, both small cell and non-small cell types. Insulin-like growth factors(IGFs) are important mitogenic and anabolic peptides, both in vivo and in vitro, and are thought to be significant autocrine-paracrine factors involved in normal and malignant cell proliferation. In this study, the degree of expression of IGF-1 on the immunohistochemical staining in human non-small cell lung cancer(NSCLC) cells and small cell lung cancer (SCLC) cells were investigated. Methods : Immunohistochemical staining for IGF-1 was performed in 15 cases of small cell carcinoma, 15 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 12 cases of bronchoalveolar carcinoma. Results : The expression of IGF-1 on the immunohistochemical staining significantly increased in NSCLC cells than in SCLC cells. Conclusion : These results suggest the expression of IGF-1 in human lung cancer cells. The immunohistochemical staining of IGF-1 in lung cancer cell lines may assist in the differentiation of NSCLC and SCLC.
All-trans retinoic acid (AtRA) induces growth inhibition and apoptosis in a variety of tumer cells, including MCF-7 cells. Insulin-like growth factors (IGFs) system has been reported to be associated with the development of cancer. Although MCF-7 cell with AtRA is to be the major stimulus for the cell growth and apoptosis, the mechanism of insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3) system remains to be elucidated. Thus, this study was conducted to the effect of AtRA on the gene expression and level of IGF-I and IGFBP-3. In addition, we investigated the involvement of PKC-${\delta}$ on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA(${\geq}10^{-7}M$) decreased the IGF-1 secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cells. Especially, the treatment of AtRA at 72 hours caused a significant reduction in the IGF-I secretion and mRNA expressions but increment in IGFBP-3 secretion and mRNA expressions (p < 0.05). $10^{-7}M$ AtRA activated PKC-${\delta}$ that is one among PKC-$\iota$, ${\alpha}$, ${\lambda}$ and ${\delta}$ in MCF-7 cell. Rotllerin, a PKC-${\delta}$ inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of lGFBP-3 and mRNA expressions in MCF-7 cell. Together, AtRA inhibited the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cell. Furthermore, AtRA-induced alteration of IGF-I, IGFBP-3 secretion, and the gene expressions were mediated via PKC-${\delta}$ activity.
Kim, Jung-Gu;Suh, Chang-Seok;Kim, Seok-Hyun;Choi, Young-Min;Moon, Shin-Yong;Lee, Jin-Yong
Clinical and Experimental Reproductive Medicine
/
v.26
no.3
/
pp.331-338
/
1999
The purposes of this study were to evaluate the effects of insulin-like growth factor (IGF)s in peritoneal fluid (PF) from patients with and without endometriosis on the proliferation of endometrial stromal cells and to investigate the effects of type I IGF receptor antibody on the response of endometrial stromal cells to PF from patients with endometriosis. IGFs in PF from patients with endometriosis (n=14) and without endometriosis (n=10) were measured by immunoradiometric assay and PF samples were divided into low IGF-I PF group (less than 85 ng/ml) and high IGF-I PF group (more than 85 ng/ml). Endometrial stromal cells from patients without endometriosis were cultured in serum free media in the presence or absence of 1 % PF and thymidine incorporation test were used to evaluate the proliferation of endometrial stromal cells. Also cultures were incubated with type I IGF receptor monoclonal antibody (${\alpha}IR_3$) before adding PF. PF from patients with endometriosis and without endometriosis increased thymidine incorporation in endometrial stromal cells. In patients with endometriosis, high IGF-I PF group had high IGF-II levels and resulted in higher thymidine incorporation than low IGF-I PF group but no significant difference in increase in thymidine incorporation between high IGF-I and low IGF-I PF group was noted in patients without endometriosis. There was not a significant correlation between increase in thymidine incorporation and IGF-I levels in PF from patients without endometriosis but in PF from patients with endometriosis. Preincubation with ${\alpha}IR_3$ significantly inhibited the mitogenic response of endometrial stromal cells to PF. Our data indicate that IGF-I in PF may be involved in the growth of ectopic endometrium in patients with endometriosis.
The aim of present study was to characterize phosphate uptake and to investigate the mechanism for the insulin and insulin-like growth factor(IGF) stimulation of phosphate uptake in primary cultured rabbit renal proximal tubule cells. Results were as follows : 1. The primary cultured proximal tubule cells had accumulated $6.68{\pm}0.70$ nmole phosphate/mg protein in the presence of 140 mM NaCl and $2.07{\pm}0.17$ nmole phosphate/mg protein in the presence of 140 mM KCl during a 60 minute uptake period. Raising the concentration of extracellular phosphate to 100 mM$(48.33{\pm}1.76\;pmole/mg\;protein/min)$ induced decrease in phosphate uptake compared with that in control cells maintained in 1 mM phosphate$(190.66{\pm}13.01\;pmole/mg\;protein/min)$. Optimal phosphate uptake was observed at pH 6.5 in the presence of 140 mM NaCl. Phosphate uptake at pH 7.2 and pH 7.9 decreased to $83.06{\pm}5.75%\;and\;74.61{\pm}3.29%$ of that of pH 6.5, respectively. 2. Phosphate uptake was inhibited by iodoacetic acid(IAA) or valinomycin treatment $(62.41{\pm}4.40%\;and\;12.80{\pm}1.64%\;of\;that\;of\;control,\;respectively)$. When IAA and valinomycin were added together, phosphate uptake was inhibited to $8.04{\pm}0.61%$ of that of control. Phosphate uptake by the primary proximal tubule cells was significantly reduced by ouabain treatment$(80.27{\pm}6.96%\;of\;that\;of\;control)$. Inhibition of protein and/or RNA synthesis by either cycloheximide or actinomycin D markedly attenuated phosphate uptake. 3. Extracellular CAMP and phorbol 12-myristate 13 acetate(PMA) decreased phosphate uptake in a dose-dependent manner in all experimental conditions. Treatment of cells with pertussis toxin or cholera toxin inhibited phosphate uptake. cAMP concentration between $10^{-6}\;M\;and\;10^{-4}\;M$ significantly inhibited phosphate uptake. Phosphate uptake was blocked to about 25% of that of control at 100 ng/ml PMA. 3-Isobutyl-1-methyl-xanthine(IBMX) inhibited phosphate uptake. However, in the presence of IBMX, the inhibitory effect of exogenous cAMP was not significantly potentiated. Forskolin decreased phosphate transport. Acetylsalicylic acid did not inhibit phosphate uptake. The 1,2-dioctanoyl-sn-glycorol(DAG) and 1-oleoyl-2-acetyl-sn- glycerol(OAG) showed a inhibitory effect. However, staurosporine had no effect on phosphate uptake. When PMA and staurosporine were treated together, inhibition of phosphate uptake was not observed. In conclusion, phosphate uptake is stimulated by high sodium and low phosphate and pH 6.5 in the culture medium. Membrane potential and intracellular energy levels are also an important factor fer phosphate transport. Insulin and IGF-I stimulate phosphate uptake through a mechanisms that involve do novo protein and/or RNA synthesis and decrease of intracellular cAMP level. Also protein kinase C(PKC) is may play a regulatory role in transducing the insulin and IGF-I signal for phosphate transport in primary cultured proximal tubule cells.
Koe, Yang Sim;Lee, Soo Yeon;Kim, Won;Cho, Soo Chul;Hwang, Pyoung Han;Kim, Jung Soo;Lee, Dae-Yeol
Clinical and Experimental Pediatrics
/
v.46
no.7
/
pp.687-694
/
2003
Purpose : Regeneration and repair after ischemic renal injury appears to be modulated by circulating or locally produced growth factors. This study examined the changes of serum insulin like growth factor(IGF-I) and renal expression of IGF-I and II, vascular endothelial growth factor(VEGF), transforming growth $factor-{\beta}$($TGF-{\beta}$), and connective tissue growth factor(CTGF) during the active regeneration period after acute ischemic injury. Methods : Sera and kidney tissue samples(whole kidney, cortex, outer medullae and inner medullae) were obtained before and after one, three, five and seven days of 40 minutes bilateral renal pedicle clamping. Acute renal failure was assessed by measuring the concentration of serum creatinine. Serum IGF-I level was measured by radioimmunoassay. The mRNA expression in kidney was measured by RT-PCR. The distribution of IGF-I and CTGF was detected by immunohistochemistry. Resuts : Serum IGF-I concentration after one day following acute ischemic renal injury was significantly decreased compared to preischemic value. The mRNA levels of IGF-I, IGF-II, $TGF-{\beta}1$ and VEGF in whole kidney were temporally decreased on day one of ischemic injury. IGF-I and IGF-II expressions in outer medullae were significantly decreased on day one after ischemic injury. $TGF-{\beta}1$, CTGF and VEGF expressions were markedly decreased in medullae after one day of ischemic injury compared to other kidney sections. IGF-I was markedly decreased in cortical tubules on day one of uremic rat. CTGF was markedly increased on tubule within three days of ischemic injury. Conclusion : These findings suggest that IGFs, $TGF-{\beta}1$ and CTGF may involve in the pathogenesis or the recovery from acute ischemic renal injury.
Kim, Sun Young;Kim, Se Rim;Lee, Jung Chang;Yi, Ho Keun;Lee, Dae Yeol;Hwang, Pyoung Han
Clinical and Experimental Pediatrics
/
v.49
no.4
/
pp.431-438
/
2006
Purpose : Insulin-like growth factor binding protein(IGFBP)-3 has been known as a tumor suppressor gene, and its anti-tumor function was divided into insulin-like growth factor(IGF)-dependent and IGF-independent mechanism. In IGF-independent mechanism, IGFBP-3 directly interacts with a cell without binding of IGFs, becoming an interesting object in oncology. Several studies demonstrate that one of the well-known tumor suppressor genes, p53, induces directly IGFBP-3 transcription, and the increment of IGFBP-3 expression induces apoptosis of many cancer cells. Recently, the anti-tumor mechanisms of IGFBP-3 have been reported, but post-translational modification of IGFBP-3 and its anti-tumor mechanism are not well known. In this study, we examined whether p53 regulated the glycosylation of IGFBP-3, and analysed the meaning of IGFBP-3 glycosylation related to the apoptosis of cancer cell. Methods : The p53-mutated status of MDA-MB-231 human breast cancer cells was used in this experiment. The expression and glycosylation of IGFBP-3 were tested by Western blot analysis after infection of adenovirus mediated Ad/p53 and/or Ad/IGFBP-3. Results : Ad/p53 infected cells resulted in growth retardation and the induced apoptosis. p53 induced direct expression and glycosylation of IGFBP-3. The increase of glcosylated IGFBP-3 was able to promote cellular apoptosis, and the glycosylation of IGFBP-3 was more activated by the double treatment of Ad/p53 and Ad/IGFBP-3. Conclusion : From this study, the anti-tumor activity of IGFBP-3 was shown to improve the stabilization of IGFBP-3 through the increment of glycosylation of IGFBP-3 by p53. This result suggests that the combined gene therapy of p53 and IGFBP-3 may appropriate treatment of cancer.
Background: Cell growth is a balance between cell proliferation and cell death. Insulin-like growth factor-I(IGF-I), which binds IGF-I receptor(IGF-IR), mediates cellular proliferation as a potent mitogen. IGF binding protein-3(IGFBP-3) as a circulating major IGFBP can inhibit or enhance the effects of IGF-I on cellular growth by binding IGFs. Methods: We investigated the expressions of mRNA of IGF-I and IGF-IR by northern blot and phosphorylation of IGF-IR with the treatment of IGF-I by western blot in 3T3 fibroblast cells. The cellular proliferations of 3T3 cells with the treatments of IGF-I were evaluated using $^3H$-thymidine incorporation and MTT assay. Also to observe the effect of IGFBP-3 on cellular proliferation, 3T3 cells were treated with anti-IGFBP-3 and ${\alpha}IR_3$(monoclonal antibody to IGF-IR) alone or in combination. Results: Our results demonstrated that 3T3 cells showed mRNA expressions of IGF-I and IGF-IR and the IGF-I increased phosphorylation of IGF-IR. The treatments of 3T3 cells with IGF-I increased cellular proliferation in 5 % and 1 % seruma-containing media, not in serum-free media. The addition of anti-IGFBP-3 to neutralize IGFBP-3 showed 2-fold increase of cellular proliferation, and also co-incubation of anti-IGFBP-3 and ${\alpha}IR_3$ together showed similar increase of cellular proliferation in 3T3 cells. Interestingly, when the cells were pretreated with ${\alpha}IR_3$ for 4 hr, prior to the simultaneous addition of ${\alpha}IR_3$ and anti-IGFBP-3, anti-IGFBP-3-mediated cellular proliferation was decreased to control level. All of these results suggest that free IGF-I released from IGF-I/IGFBP-3 complex would be involved in the cellular proliferation. Conclusion: IGF-I is a mitogen through the activation of IGF-IR in 3T3 cells, and IGFBP-3 could be a potent inhibitor for IGF-I action by binding IGF-I.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.