Anticancer effects on TACC3 by treatment of paclitaxel in HPV-18 positive cervical carcinoma cells.

Yim, Eun-Kyoung,Tong, Seo-Yun,Ho, Eun-Mi,Bae, Jeong-Hoon,Um, Soo-Jong,Park, Jong-Sup National Hellenic Research Foundation 2009 ONCOLOGY REPORTS Vol.21 No.2

<P>Previously, we used proteome analysis to identify transforming acidic coiled coil (TACC) 3 as a protein that is down-regulated upon paclitaxel treatment in cervical cancer cells. TACC3 mRNA and protein levels decreased after paclitaxel treatment in a time- and dose-dependent manner, and the transactivation of TACC3 promoter was dramatically diminished by paclitaxel. Importantly, paclitaxel treatment and knockdown of TACC3 by siRNA led to a synergistic enhancement of significant G2/M phase arrest and apoptosis in HeLa cells. In contrast to TACC3-deficient cells, paclitaxel treatment of mTACC3-overexpressing cells failed to induce G2/M phase arrest, cell growth inhibition, and apoptotic cell death. We studied the associated gene in mTACC overexpressed cells using microarray. From these results, numerous genes have been identified as being associated with tumor progression (Ppia, TMSB10, Annexin A2, rab31, prostaglandin E2-EP2, UHRF1), chemoresistance (Akt, Plk-1, MAP kinase) and metastasis (MMP9, PECAM-1) in mTACC3 overexpressed HeLa cells. Thus, TACC3 is thought to be the critical molecule in mediating the anticancer mechanisms of paclitaxel in p53 inactivated cells by inducing G2/M arrest and apoptosis. And our data suggested that the overexpression of TACC3 may be associated with the mechanisms of chemoresistance, tumor progression, cell proliferation and metastasis.</P>

Proteome Analysis of Differential Protein Expression in Cervical Cancer Cells after Paclitaxel Treatment

Eun-Kyoung Yim,Jun-Sang Bae,Seung-Bak Lee,Keun-Ho Lee,Chan-Joo Kim,Sung-Eun Namkoong,Soo-Jong Um,Jong-Sup Park 대한암학회 2004 Cancer Research and Treatment Vol.36 No.6

Purpose: It is well known that infection with HPV (human papillomavirus) is the main cause of cervical cancer and certain types of HPV are recognized as carcinogens. At present, there is little information regarding the antineoplastic mechanism of paclitaxel against cervical carcinoma cells. We thus tried to analyze differential protein expression and antineoplastic mechanism-related proteins after paclitaxel treatment on cervical cancer cells by using a proteomic analysis and to investigate the mechanism of action. Materials and Methods: Using proteomics analysis including 2-DE and MALDI-TOF-MS, we detected the antineoplastic mechanism-related proteins. Then, we performed western blot analysis for apoptosis- and transformation- related proteins to confirm expression patterns derived from proteome analysis after paclitaxel treatment. Results: We identified several cellular proteins that are responsive to paclitaxel treatment in HeLa cells using proteomics methods. Paclitaxel treatment elevated main-ly apoptosis, immune response and cell cycle check point- related proteins. On the other hand, paclitaxel treatment diminished growth factor/oncogene-related proteins and transcription regulation-related proteins. Also, in the HPV-associated cervical carcinoma cells, paclitaxel demonstrated anti-proliferative activity through the membrane death receptor-mediated apoptotic pathway and the mitochondrial-mediated pathway. Conclusion: Identification and characterization of functionally modulated proteins involved in anti-cancer regulatory events should lead to a better understanding of the long-term actions of paclitaxel at the molecular level and will contribute to the future development of novel therapeutic drug treatments based upon current therapies.(Cancer Res Treat. 2004;36:395-399)

Novel Interaction between HPV E6 and BARD1 (BRCA1-Associated Ring Domain 1) and Its Biologic Roles

Yim, Eun-Kyoung,Lee, Keun-Ho,Myeong, Jin,Tong, Seo-Yun,Um, Soo-Jong,Park, Jong-Sup Mary Ann Liebert, Inc 2007 DNA and cell biology Vol.26 No.10

<P>Human papillomaviruses (HPVs), which are associated with the majority of cervical cancers, encode a transforming protein, E6, which interacts with the p53 tumor suppressor protein. There is a wide effort focused on searching for the target of the involvement of p53-independent HPV 16 E6-interacting proteins. We identified Breast Cancer 1 Gene (BRCA1)-associated ring domain protein 1 (BARD1) as a binding partner of E6 and investigated its biological function in cervical cancer cells. In vivo co-immunoprecipitation assay was performed to determine whether E6-BARD1 interaction occurred. We then used a degradation assay to determine whether E6-mediated inactivation of BARD1 transactivation function was associated with BARD1 degradation. A mutation assay revealed the site of interaction of E6 with BARD1. The effect of BARD1 on p53 transcriptional activity was tested using BARD1 knockdown and overexpression systems. BARD1 was not degraded by E6, and, instead, formed a physical complex with E6. Moreover, the mutations of the metal motif zinc-finger region decreased the ability of E6 to interact with BARD1. Transient transfection of BARD1 increased the p53-mediated activation of p21(WAF1) promoter despite the presence of E6. Additionally, the existence of BARD1 inactivated the expression of E6 in cervical cancer cells. These findings suggest that BARD1 may regulate the transcriptional activities of p53 as tumor suppressors.</P>

The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical Carcinogenesis

Eun-Kyoung Yim,Jong-Sup Park 대한암학회 2005 Cancer Research and Treatment Vol.37 No.6

Cervical cancer is one of the leading world causes of cancer morbidity and mortality in woman, with more than 98% related to a human papillomavirus (HPV) infection origin. Infection with specific subtypes of HPV has been strongly implicated in cervical carcinogenesis. The identification and functional verification of host proteinsassociated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis and the development of cervical cancerspecific markers. The advent of functional genomics and proteomics has provided hope of discovering novel biological markers for use in the screening, early diagnosis, prognostication and prediction of response to therapy. Herein, we review the studies where the profiles of host proteins associated with HPV E6 and E7 oncoproteins in cervical cancer were generated.

Characterization of Korean Leptospira interrogans Isolates by Pulsed-Field Gel Electrophoresis of Not Ⅰ Digests of DNA

Yim, Eun-Kyoung,Chang, In-Ae,Lee, Jin-Sang,Kim, Yoon-Won,Woo, Soo-Dong,Ahn, Jee-Yin,Park, Seung-Kee,Cho, Min-Kee 대한감염학회 2004 감염과 화학요법 Vol.36 No.2

배경 : 1984년 한국에서 처음으로 렙토스피라증 환자가 확진된 이래 환자와 들쥐로부터 많은 수의 렙토스피라균이 분리되었으며 혈청학적 방법에 의해 혈청형이 동정된 바 있으나 혈청형 동정에 도움이 되는 것으로 알려진 pulsed-field gel electrophoresis (PFGE)가 시행된 바는 없다. 이에 국내에서 분리된 균주들의 PFGE 양상을 파악하고 그 결과를 고전적인 혈청형 동정방법과 비교하고자 하였다. 방법 : 표준균주 29와 한국에서 분리된 분리균주 29주의 렙토스피라균을 대상으로 이들 균주들의 chromosome을 Not I 제한효소로 처리하여 contous-clamped omogeneous field (CHEF) 전기영동장치(CHEF-DRII, Bio-Rad)를 사용하여 Pulsed-Field Gel Electrophoresis를 실시하였다. 결과 : 혈청군 Icterohemorrhagiae에 속하는 17 혈청형 표준균주의 Not I 제한효소 절단양상은 각기 다르게 나타났으며, 국내 분리균주들(29주)은 세 가지의 다른 PFGE 양상을 보였다. 혈청학적인 방법에 의해 혈청형 Iai로 동정되었던 국내 분리균주들은 표준균주 Iai와 똑같은 PFGE 양상을 보였다. 혈청학적 방법으로는 혈청형 Iai와 구분되었던 AP31, CH89-19 및 N13균주도 표준균주 Iai와 같은 PFGE 양상을 보였으나, 혈청형 Iai로 동정된 바 있는 HY2 균주와 혈청형 Iai와 구분되었던 30R 균주는 표준균주 Iai와 약간 다른 PFGE 양상을 보였다. 결론 : 혈청형 Iai로 동정된 한국 분리균주들의 대부분은 표준균주 Iai와 같은 PFGE 양상을 보였다. DNA의 Not I 절단에 의한 PFGE는 분리균주의 혈청형 동정에 크게 도움이 될 뿐 아니라, 서로 관련된 혈청형 내의 유전적 다양성을 조사하는데 좋은 방법이라는 것을 확인할 수 있었다. Background : Many strains of Leptospira interrogans have been isolated in Korea since 1984. Most isolates were identified as serovar lai by serological methods. The pulsed field gel electrophoresis (PFGE) patterns of Korean isolates have not been investigated currently. Methods : 29 reference strains and 29 Korean isolates of Leptospira interrogans were characterized by PFGE. Chromosomes were digested by the Not Ⅰ restriction enzyme and subsequently PFGE was performed in CHEF-DRⅡ(Bio Rad Lab) with 3 pulse times (30 seconds 13 hours. 60 seconds 13 hours, 120 seconds 14 hours) at 150 V (4.3 V/㎝). Results : 12 serogroup reference strains and most 17 serovars reference strains in the serogroup Icterohaemoffhagie showed the unique Not I restriction patterns. Most isolates identified serologically as serovar lai showed the same PFGE patterns as the serovar lai reference strain. The strain HM3 and 18R identified serologically as new serovars yeonchon and hongchon respectively showed the same PFGE patterns as serovar lai. The strain AP31, CH88-19 and NR13 that were different from serovar lai by serological methods showed the PFGE patterns indistinguishable from serovar lai reference strain. The strain HY2 that was identified as serovar lai, and the strain 30R that was different from serovar lai serologically showed the PFGE patterns slightly different from serovar lai reference strain. Conclusion : The PFGE profile of most Korean isolates Leptospira interrogans serologically identified as serovar lai is identical to the reference strain serovar lai. PFGE analysis thus may be applied to identify serovar of isolates and to investigate the genetic diversity of related serovar.

PCR에 의한 들쥐의 렙토스피라균 감염 조사

임은경(Eun-Kyoung Yim),김윤원(Yoon-Won Kim),이진상(Jin-Sang Lee),장인애(In-Ae Chang),백락주(Luck Ju Baek),송진원(Jin-Won Song),조민기(Min-Kee Cho) 대한미생물학회 2003 Journal of Bacteriology and Virology Vol.33 No.3

The radioligands with VEGF₁₂₁ for angiogenesis of tumor

Yim, Min Su,Ryu, Eun Kyoung 대한방사성의약품학회 2018 Journal of radiopharmaceuticals and molecular prob Vol.4 No.2

Angiogenesis is the new blood vessel formation process and has known to a fundamental event of tumor growth and metastasis. Especially, vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the crucial regulators of angiogenesis in tumor. VEGF-A is one of the VEGF family and binds to endothelial cell specific VEGFR1 and VEGFR2, which are associated with tumor growth and tumor angiogenesis. $VEGF_{121}$ is more tumorigenic isomer of VEGF-A. Targeted VEGF or VEGFR molecular imaging has been widely used to enable diagnosis and monitoring of proliferation and development of angiogenic tumors. Therefore, in this review, we have focused on the radioligands with $VEGF_{121}$ for angiogenesis of tumor.

Positron emission tomography and magnetic resonance imaging

Yim, Min Su,Ryu, Eun Kyoung Korean Society of Radiopharmaceuticals and Molecul 2016 Journal of radiopharmaceuticals and molecular prob Vol.2 No.1

Molecular imaging technologies have been used to provide a new pathway for therapies and diagnosis of human disease. Especially, imaging probes have been much development in the molecular imaging field. Combining imaging probes for positron emission tomography (PET) and magnetic resonance imaging (MRI) have suggested the potential of multiple methods in living body. This review discusses the cancer or lymph node-targeting probes that are suitable for PET/MRI based diagnosis.

The targeting peptides for tumor receptor imaging

Yim, Min Su,Ryu, Eun Kyoung 대한방사성의약품학회 2016 Journal of radiopharmaceuticals and molecular prob Vol.2 No.2

Peptides have been developed for in vivo imaging probes against to the specific biomarker in the biological process of living systems. Peptide based imaging probes have been applied to identify and detect their active sites using imaging modalities, such as PET, SPECT and MRI. Especially, tumor receptor imaging with the peptides has been widely used to specific tumor detection. This review discusses the targeting peptides that have been successfully characterized for tumor diagnosis by receptor imaging.

Minke whale genome and aquatic adaptation in cetaceans

Yim, Hyung-Soon,Cho, Yun Sung,Guang, Xuanmin,Kang, Sung Gyun,Jeong, Jae-Yeon,Cha, Sun-Shin,Oh, Hyun-Myung,Lee, Jae-Hak,Yang, Eun Chan,Kwon, Kae Kyoung,Kim, Yun Jae,Kim, Tae Wan,Kim, Wonduck,Jeon, Jeon Nature Pub. Co 2014 Nature genetics Vol.46 No.1

The shift from terrestrial to aquatic life by whales was a substantial evolutionary event. Here we report the whole-genome sequencing and de novo assembly of the minke whale genome, as well as the whole-genome sequences of three minke whales, a fin whale, a bottlenose dolphin and a finless porpoise. Our comparative genomic analysis identified an expansion in the whale lineage of gene families associated with stress-responsive proteins and anaerobic metabolism, whereas gene families related to body hair and sensory receptors were contracted. Our analysis also identified whale-specific mutations in genes encoding antioxidants and enzymes controlling blood pressure and salt concentration. Overall the whale-genome sequences exhibited distinct features that are associated with the physiological and morphological changes needed for life in an aquatic environment, marked by resistance to physiological stresses caused by a lack of oxygen, increased amounts of reactive oxygen species and high salt levels.