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RISS 인기검색어
- 검색키워드
- 저자 : Whasun Kim (검색결과 40 건)
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Paradoxical expression of AHCYL1 affecting ovarian carcinogenesis between chickens and women.
Jeong, Wooyoung,Kim, Hee Seung,Kim, Yong Beom,Kim, Min A,Lim, Whasun,Kim, Jinyoung,Jang, Hyun-Jun,Suh, Dong Hoon,Kim, Kidong,Chung, Hyun Hoon,Bazer, Fuller W,Song, Yong Sang,Han, Jae Yong,Song, Gwonhw The Society 2012 Experimental biology and medicine Vol.237 No.7
<P>We investigated S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) gene expression in human epithelial ovarian cancer (EOC) using the chicken, which is the most relevant animal model. Ovarian cancer was detected in 10 of 136 laying hens (7.4%). Results of the present study indicated that AHCYL1 mRNA and protein are most abundant in the glandular epithelium of adenocarcinoma of cancerous, but not normal, ovaries of hens. In addition, bisulfite sequencing to examine methylation patterns in the promoter region of the AHCYL1 gene revealed that 30-38% of the three CpG sites were demethylated in ovarian cancer cells as compared with normal ovarian cells. Furthermore, in human ovarian cancer cells such as OVCAR-3, AHCYL1 protein was predominantly in the nucleus and had a similar expression pattern to that in chicken ovarian cancer cells. Thereafter, we examined the prognostic value of AHCYL1 expression in patients with EOC using multivariate linear logistic regression and Cox's proportional hazard analyses. In 109 human patients with EOC, 14 (12.8%), 41 (37.6%) and 54 (49.6%) patients showed weak, moderate and strong expression of AHCYL1 protein, respectively. However, intermediate or high expression of AHCYL1 protein was a favorable factor for overall responses (adjusted odds ratio, 7.23; 95% confidence interval [CI], 1.36-38.39), and for progression-free survival (adjusted hazard ratio, 0.20; 95% CI, 0.07-0.55). From these results, we conclude that AHCYL1 expression is associated with ovarian carcinogenesis as an oncogene in chickens, whereas it plays the role of tumor suppressor in human EOC, suggesting a paradoxical function of AHCYL1 in ovarian carcinogenesis.</P>
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Whasun Lim,Jee-Hye Kim,Suzie E. Ahn,Wooyoung Jeong,Jinyoung Kim,Jae Yong Han,Fuller W. Bazer,Gwonhwa Song 한국동물생명공학회(구 한국동물번식학회) 2011 발생공학 국제심포지엄 및 학술대회 Vol.2011 No.1
Serpins are a superfamily of related protease inhibitors with common structural features and inhibitory mechanisms. However, SERPINA 14 in mammals does not have inhibitory activity against most known proteases. Rather, it may have an immunoregulatory role in mammals to prevent rejection of the fetal allograft by inhibiting lymphocyte proliferation and natural killer cell function. In the pig, SERPINA14 is involved in iron transport to the fetus by binding to and stabilizing the iron-binding protein uteroferrin (ACP5). In chickens, these very little known about serpins in chickens. Therefore, we investigated the expression patterns of serpin genes in the oviduct of adult hens and in the oviduct of 37-day-old chicks treated with an estrogen analogue, diethylstilbestrol (DES). Results indicated that SERPINB3 and SERPINB11 genes were highly expressed in oviducts of DES-treated chicks, but not in oviducts of control chicks. Both SERPINB3 and SERPINB11 transcripts were localized specifically to the gland-like areas of oviducts of DES-treated chicks. Immunohistochemical analyses confirmed that SERPINB3 and SERPINB11 proteins were present in the gland-like area and luminal epithelium of the oviducts of DES-treated chicks. Collectively, the results suggest that SERPINB3 and SERPINB11 are expressed in response to estrogens and they have distinct functions related to development and differentiation of the mature oviduct in hens.
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SERPINB3 in the Chicken Model of Epithelial Ovarian Cancer
Whasun Lim,Hee Seung Kim,Jinyoung Kim,Wooyoung Jeong,Jin Young Lee,Chul Hong Lim,Seung Min Bae,Jae Yong Han,Fuller W. Bazer,Gwonhwa Song 한국동물번식학회 2012 Reproductive & Developmental Biology(Supplement) Vol.36 No.2s
SERPINB3 (also known Squamous cell carcinoma antigen 1, SCCA1) is involved in apoptosis, immune response, cell migration and invasiveness of cells. It has been investigated in various types of squamous cell carcinoma. Therefore we investigated the functional role of SERPINB3 gene in human epithelial ovarian cancer (EOC) using laying hens, the most relevant animal model. In 136 laying hens, EOC was found in 10 (7.4%). We compared the expression and localization of SERPINB3 using RT-PCR, quantitative RT-PCR, in situ hybridization and immunohistochemistry, and SERPINB3 activation was detected in chicken and human ovarian cancer cell lines using immunofluorescence microscopy. Thereafter, we examined the prognostic value of SERPINB3 expression in patients with EOC by multivariate linear logistic regression and Cox’ proportional hazard analyses. In present study, SERPINB3 mRNA was induced in cancerous ovaries (p< 0.01), and it was only expressed in the glandular epithelium(GE) of cancerous ovaries of laying hens. SERPINB3 protein was localized predominantly to the nucleus of glandular epithelium in cancerous ovaries of laying hens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 15 (13.8%), 66 (60.6%) and 28 (25.7%) of those patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance (adjusted OR, 5.94; 95% Confidence Limits, 1.21-29.15). Therefore SERPINB3 may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC. This research was funded by the World Class University (WCU) program (R31-10056), Basic Science Research Program (2010- 0013078) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology and by the Next-Generation BioGreen 21 Program (No.PJ008142), Rural Development Administration, Republic of Korea.
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Differential Expression of SERPINs in the Chicken Oviduct
Whasun Lim(임화선),Jihye Kim,Suzie E. Ahn,Wooyoung Jeong,Jinyoung Kim,Jin Won Choi,Jae Yong Han,Fuller W. Bazer,Gwonhwa Song 한국가금학회 2010 한국가금학회 정기총회 및 학술발표회 Vol.27 No.-
Serpins are a superfamily of relating to inhibit protease with common structural features and inhibitory mechanisms. It is also known as ov-serpins in chicken which are ovalbumin and secreted chicken oviduct protein. However, to our knowledge, it is relatively little known about serpins in chickens. In this study, we investigated the expression patterns of serpin genes in the adult chicken oviduct and also the neonatal oviduct of 37-day-old chicks which were treated with an estrogen analogue, diethylstilbestrol (DES). As results SERPINB3 and SERPINB11 genes were highly expressed in DES-treated oviducts but not in non-treated oviduct. Localization of SERPINB3 and SERPINB11 transcripts were specifically found in the gland-like area of adult chicken oviduct. Collectively, our current data suggest that SERPINB3 and SERPINB11 may have distinct functions in the differentiation processes dependent of steroid hormone regulation in the hen oviduct.
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Lim, Whasun,Kim, Ji-Hye,Ahn, Suzie E,Jeong, Wooyoung,Kim, Jinyoung,Bazer, Fuller W,Han, Jae Yong,Song, Gwonhwa Society for the Study of Reproduction [etc.] 2011 BIOLOGY OF REPRODUCTION Vol.85 No.6
<P>Serpins, a group of proteins with similar structural and functional properties, were first identified based on their unique mechanism of action: their inhibition of proteases. While most serpins have inhibitory roles, certain serpins are not involved in canonical proteolytic cascades but perform diverse functions including storage of ovalbumin in egg white, transport of hormones (thyroxine- and cortisol-binding globulin), and suppression of tumors. Of these, serpin peptidase inhibitor, clade B, member 11 (SERPINB11) is not an inhibitor of known proteases in humans and mice, and its function is unknown. In the present study, the SERPINB11 gene was cloned, and its expression profile was analyzed in various tissues from chickens. The chicken SERPINB11 gene has an open reading frame of 1346 nucleotides that encode a protein of 388 amino acids that has moderate homology (38.8%-42.3%) to mammalian SERPINB11 proteins. Importantly, SERPINB11 mRNA is most abundant in the chicken oviduct, specifically luminal and glandular epithelia, but it was not detected in any other chicken tissues of either sex. We then determined effects of diethylstilbestrol (DES; a synthetic nonsteroidal estrogen) on SERPINB11 expression in the chicken oviduct. Treatment of young chicks with DES induced SERPINB11 mRNA and protein only in luminal and glandular epithelial cells of the oviduct. Collectively, these results indicate that the novel estrogen-induced SERPINB11 gene is expressed only in epithelial cells of the chicken oviduct and implicate SERPINB11 in regulation of oviduct development and differentiated functions.</P>
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Avian SERPINB11 gene: a marker for ovarian endometrioid cancer in chickens.
Lim, Whasun,Kim, Ji-Hye,Ahn, Suzie E,Jeong, Wooyoung,Kim, Jinyoung,Bazer, Fuller W,Han, Jae Yong,Song, Gwonhwa The Society 2012 Experimental biology and medicine Vol.237 No.2
<P>As serine and cysteine proteinase inhibitors, serpins, such as SERPINB5, cause ovarian, colorectal and pancreatic adenocarcinomas. We identified SERPINB11 as a novel estrogen-induced gene in chickens during oviduct development. The chicken is a unique animal model for research on human ovarian cancer, because it spontaneously develops epithelial cell-derived ovarian cancer as in women. Therefore, this study investigated the expression pattern, CpG methylation status, and miRNA regulation of the SERPINB11 gene in normal and cancerous ovaries from chickens. Our results indicate that SERPINB11 is most abundant in the glandular epithelium of endometrioid adenocarcinoma of cancerous, but not normal, ovaries of hens. In addition, bisulfite sequencing revealed that about 30% of -110 CpG sites are methylated in ovarian cancer cells, whereas -110 CpG sites are demethylated in normal ovarian cells. Next, we determined whether miR-1582 influences SERPINB11 expression via its 3'UTR and found that it does not directly target the 3'UTR of SERPINB11 mRNA. Therefore, it is unlikely that post-transcriptional regulation influences SERPINB11 expression in the chicken ovary. On the other hand, in human ovarian cancer cells such as OVCAR-3, SKOV-3 and PA-1 cells, immunoreactive SERPINB11 protein was predominant in the cytoplasm and had a similar expression pattern to that in chicken ovarian cancer cells. Collectively, these results suggest that SERPINB11 is a biomarker for chicken ovarian endometrioid carcinoma that could be used for diagnosis and monitoring effects of therapies for the disease in women.</P>
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Exosomes as Therapeutic Vehicles for Cancer
Whasun Lim,Han-Soo Kim 한국조직공학과 재생의학회 2019 조직공학과 재생의학 Vol.16 No.3
BACKGROUND: Exosomes are membrane-enclosed extracellular vesicles implicated in cell–cell communication. Exosomes contain proteins, mRNAs, non-coding RNAs (miRNAs and lncRNAs) and lipids that are derived from producing cells. These nano-sized vesicles are present in biofluids including blood, urine, saliva, amniotic fluid, semen and conditioned media of cultured cells. METHODS: This review summarizes current progress on the strategies of development of diagnostic biomarkers and drug loading onto exosomes for overcoming cancer progression. RESULTS: A number of studies indicate that the exosome appears to be a key player in tissue repair and regeneration of in a number of animal disease models. In addition, alterations of the molecular profiles in exosomes are known to be correlated with the disease progression including cancer, suggesting their usefulness in disease diagnosis and prognosis. Studies utilizing engineered exosomes either by chemical or biological methods have demonstrated promising results in a number of animal models with cancer. CONCLUSION: Understanding the molecular and cellular properties of exosomes offer benefits for cancer diagnosis by liquid biopsy and for their application in therapeutic drug delivery systems. Studies have shown that genetic or molecular engineering of exosomes augmented their target specificity and anticancer activity with less toxicity. Thus, deeper understanding of exosome biology will facilitate their therapeutic potential as an innovative drug delivery system for cancer.
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