• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.248-255
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• 2005

To understand the response of cancer cells to anticancer drugs at the gene expression level, we examined the gene expression changes in response to five anticancer drugs, 5-fluorouracil, cytarabine, cisplatin, paclitaxel, and cytochalasin D in NCI-H460 human lung cancer cells. Of the five drugs, 5-fluorouracil had the most distinctive gene expression signature. By clustering genes whose expression changed significantly, we identified three clusters with unique gene expression patterns. The first cluster reflected the up-regulation of gene expression by cisplatin, and included genes involved in cell death and DNA repair. The second cluster pointed to a general reduction of gene expression by most of the anticancer drugs tested. A number of genes in this cluster are involved in signal transduction that is important for communication between cells and reception of extracellular signals. The last cluster represented reduced gene expression in response to 5-fluorouracil, the genes involved being implicated in DNA metabolism, the cell cycle, and RNA processing. Since the gene expression signature of 5-fluorouracil was unique, we investigated it in more detail. Significance analysis of microarray data (SAM) identified 808 genes whose expression was significantly altered by 5-fluorouracil. Among the up-regulated genes, those affecting apoptosis were the most noteworthy. The down-regulated genes were mainly associated with transcription-and translation-related processes which are known targets of 5-fluorouracil. These results suggest that the gene expression signature of an anticancer drug is closely related to its physiological action and the response of caner cells.

• 한국발생생물학회지:발생과생식
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• 제18권4호
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• pp.293-300
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• 2014

Direct cell-cell communication through connexin (Cx) complexes is a way to achieve functional accordance of cells within a tissue or an organ. The initial segment (IS), a part of the epididymis, plays important roles in sperm maturation. Steroid hormones influence on expression of a number of genes in the IS of adult animals. However, developmental effect of sex hormones on the gene expression in the IS has not been examined. In this study, estradiol benzoate (EB, an estrogen agonist) or flutamide (Flu, an androgen antagonist) was exogenously administrated at 1 week of postnatal age, and expressional changes of Cx genes in the IS were determined at 4 months of age by a quantitative real-time PCR analysis. Treatment of EB at $0.015{\mu}g/kg$ body weight (BW) increased expression of Cx30.3, 31.1, and 43 genes. However, treatment of 1.5 mg EB/kg BW resulted in expressional decreases of Cx31, 32, and 45 genes and caused increases of Cx30.3 and 43 gene expression. Significant decreases of Cx31, 31.1, 32, 37, and 45 gene expression were detected with a treatment of $500{\mu}g\;Flu/kg$ BW, while expression of Cx43 gene was significantly increased with a treatment of $500{\mu}g\;Flu/kg$ BW. A treatment of $50{\mu}g\;Flu/kg$ BW led to significant increases of Cx30.3, 32, 37, 40, and 43 gene expression. These findings imply that exogenous exposure of steroidal hormones during the early developmental period would result in aberrant expression of Cx genes in the adult IS.

• 한국발생생물학회지:발생과생식
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• 제19권2호
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• pp.69-77
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• 2015

Cell-cell direct communication through channel-forming molecules, connexin (Cx), is essential for a tissue to exchange signaling molecules between neighboring cells and establish unique functional characteristics during postnatal development. The corpus epididymis is a well-known androgen-responsive tissue and involves in proper sperm maturation. In the present research, it was attempted to determine if expression of Cx isoforms in the corpus epididymis in the adult is modulated by exposure to estrogenic or anti-androgenic compound during the early postnatal period. The neonatal male rats at 7 days of age were subcutaneously injected by estradiol benzoate (EB) at low-dose ($0.015{\mu}g/kg$ body weight) or high-dose ($1.5{\mu}g/kg$ body weight) or flutamide (Flu) at low-dose ($500{\mu}g/kg$ body weight) or high-dose (50 mg/kg body weight). The corpus epididymis collected at 4 months of age was subjected to evaluate expressional changes of Cx isoforms by quantitative real-time PCR. Treatment of low-dose EB resulted in increases of Cx32, Cx37, and Cx45 transcript levels, while exposure to high-dose EB decreased expression of Cx26, Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45. Treatments of Flu caused significant decreases of expression of all examined Cx isoforms, except Cx37 and Cx43 shown no expressional change with high-dose Flu treatment. These findings imply that expression of most Cx isoforms present in the corpus epididymis would be transcriptionally regulated by actions of androgen and/or estrogen during postnatal period.

• 한국발생생물학회지:발생과생식
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• 제13권3호
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• pp.133-143
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• 2009

Pivotal roles of steroid hormones in uterine endometrial function are well established from the mouse models carrying the null mutation of their receptors. Literally androgen belongs to male but interestingly it also detected in female. The fluctuations of androgen levels are observed during reproductive cycle and pregnancy, and the functional androgen receptor is expressed in reproductive organs including uterus. Using high throughput methodology, the downstream genes of androgen have been isolated and revealed correlations between other steroid hormones. In androgen-deficient mice, uterine responses to exogenous gonadotropins are impaired and the number of pups per litter is reduced dramatically. As expected androgen has important role in decidual differentiation through AR. It regulates specific gene network during those cellular responses. Recently we examined the effects of steroid hormonal complex containing high level of androgen. Interestingly, on the contrary to the androgen-alone administration, the hormonal complex did not disturb the decidual reaction and the pubs did not show any morphological abnormality. It is suspected that the complexity of communication between other steroid hormone and their receptors are the reasons. In summary, androgen exists in female blood and it suggests the importance of androgen in female reproduction. However, the complex interactions with other hormones are not fully understood compared with estrogen and progesterone. The further studies to evaluate the possible role of androgen are needed and important to provide the in vivo rational for the prevention of associated pregnancy complications and help human's health.

• 한국발생생물학회지:발생과생식
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• 제21권4호
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• pp.379-389
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• 2017

Connexin (Cx) involves in the regulation of various physiological functions of tissue by forming a channel, a gap junction which allows direct cell-cell communication, between adjacent cells. The effect of a single subcutaneous treatment of estradiol benzoate (EB) or flutamide (Flu) at the weaning age on the expression of Cx isoforms in the adult caput epididymis was evaluated in this research. Using quantitative real-time PCR analysis, a low-dose of EB [$0.015{\mu}g/kg$ body weight (BW)] caused significant decreases of Cx30.3, Cx32, Cx40, Cx43, and Cx45 mRNA levels and no change of Cx26, Cx31, Cx31.1, Cx37 transcript levels. The treatment of a high-dose EB ($1.5{\mu}g/kg\;BW$) resulted in reduced expression of Cx30.3, Cx31, Cx43, and Cx45 but increased expression of Cx37 and Cx40. Expression of all Cx isoforms examined, except Cx31, was significantly increased by the treatment of a low-dose Flu ($500{\mu}g/kg\;BW$). However, the treatment of a high-dose Flu (5 mg/kg BW) led significant expressional suppression of Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45 but an increase of Cx37 transcript level. With the comparison of previous findings, the expression of Cx isoforms in the adult epididymis after the exposure to EB or Flu is likely differentially regulated in regional-specific and/or exposed postnatal age-specific manner.

• 한국정보통신학회논문지
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• 제18권2호
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• pp.482-487
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• 2014

본 연구는 testosterone이 지방세포생성에 미치는 영향과 그것에 대한 분자생물학적 조절기전을 역전사-중합효소 연쇄반응과 일시적인 형질전환 분석을 통해 조사하였다. 정소절제수술 마우스(CAST)에 비해 testosterone이 처리된 정소절제수술 마우스(CAST+T)는 백색지방조직 무게와 지방세포 특이유전자($PPAR{\gamma}$와 aP2)의 발현이 감소되었다. In vivo 결과와 일치되게, testosterone 처리는 분화된 3T3-L1세포에서의 triglyceride축적과 지방세포 특이유전자($PPAR{\gamma}$와 aP2)의 발현을 억제시켰다. Testosterone에 의해 활성화된 androgen receptor(AR)는 $PPAR{\gamma}$ transfection에 의해 유도된 luciferase reporter gene 활성을 억제하였다. 따라서 본 연구결과는 testosterone이 AR을 통해 지방세포분화에 대한 $PPAR{\gamma}$의 작용을 억제 조절한다는 것을 시사하고 있다.

• 한국정보통신학회논문지
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• 제17권5호
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• pp.1239-1244
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• 2013

임상 의료 분야에서 질병 진단 및 치료를 위해서는 분자 수준(프로틴, DNA 등)의 크기 뿐만 아니라, 세포 수준에 대한 분석이 필요하다. 많은 경우 실험 샘플이 시간에 따라 변질되기 때문에 정확한 분석을 위해서는 빠른 분석과 실시간 데이터가 필요하다. 본 연구에서는 나노 마이크로 크기의 세포내 단백질이나 DNA의 변화 과정 등을 촬영할 수 있는 3차원 형광 관측 장치를 제작하고 이로부터 얻은 형광 이미지를 실시간 통합 관리 및 분석하기 위한 서버 클라이언트 기반의 형광 이미지 분석 시스템을 구축하였다. 시스템은 형광 관측 장치와 소프트웨어 그리고 형광 이미지를 실시간으로 분석할 수 있는 모바일 프로그램으로 구성된다. 개발된 시스템은 의료인이 시공간의 제약 없이 응급환자의 샘플에서 획득한 형광이미지를 실시간으로 전송받아 분석 및 진단을 내릴 수 있도록 해 주므로 유비쿼터스 헬스 구현에 활용할 수 있다.

• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.415-421
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• 2018

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature. Methods: Eighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Başkent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method. Results: No significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found. Conclusion: Knowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey.

• BMB Reports
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• 제54권10호
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• pp.497-504
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• 2021

EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx-Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2- BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC.

• Molecules and Cells
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• 제44권11호
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• pp.784-794
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• 2021

Leiomyosarcoma (LMS) is a mesenchymal malignancy with a complex karyotype. Despite accumulated evidence, the factors contributing to the development of LMS are unclear. Here, we investigated the role of tight-junction protein 1 (TJP1), a membrane-associated intercellular barrier protein during the development of LMS and the tumor microenvironment. We orthotopically transplanted SK-LMS-1 cells and their derivatives in terms of TJP1 expression by intramuscular injection, such as SK-LMS-1 Sh-Control cells and SK-LMS-1 Sh-TJP1. We observed robust tumor growth in mice transplanted with LMS cell lines expressing TJP1 while no tumor mass was found in mice transplanted with SK-LMS-1 Sh-TJP1 cells with silenced TJP1 expression. Tissues from mice were stained and further analyzed to clarify the effects of TJP1 expression on tumor development and the tumor microenvironment. To identify the TJP1-dependent factors important in the development of LMS, genes with altered expression were selected in SK-LMS-1 cells such as cyclinD1, CSF1 and so on. The top 10% of highly expressed genes in LMS tissues were obtained from public databases. Further analysis revealed two clusters related to cell proliferation and the tumor microenvironment. Furthermore, integrated analyses of the gene expression networks revealed correlations among TJP1, CSF1 and CTLA4 at the mRNA level, suggesting a possible role for TJP1 in the immune environment. Taken together, these results imply that TJP1 contributes to the development of sarcoma by proliferation through modulating cell-cell aggregation and communication through cytokines in the tumor microenvironment and might be a beneficial therapeutic target.