• Asian-Australasian Journal of Animal Sciences
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• 제15권8호
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• pp.1198-1203
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• 2002

To understand molecular mechanisms involved in bovine mammary gland growth, expression of stat5a gene was examined in bovine mammary tissues. We found that stat5a gene was highly induced at pregnant 7 and 8 months compared to virgin mammary tissues. To examine function of bovine stat5a in mammary epithelial cell proliferation, stat5a expression vector was transfected into mammary epithelial HC11 cells. Cell proliferation rate in stat5a gene-transfected cells was 26%, 95% and 85% higher at 24 h, 48 h and 72 h after seeding, respectively, compared to control vector-transfected cells. Results demonstrate that bovine stat5a enhances proliferation of mammary epithelial cells.

• 통합자연과학논문집
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• 제17권1호
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• pp.13-20
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• 2024

Female breast cancer is the fifth highest cause of mortality. Breast cancer is the most prevalent type of cancer in women globally, while it can also affect men. STAT5A plays a role in its development and progression. Given that activation of STAT5a is frequently linked to the growth and progression of tumors, STAT5a has been identified as a possible target for the therapy of several cancers. STAT5A, in particular, has proven to be overexpressed in various breast cancer cell lines and tumors, and it has been associated to the promotion of tumour cell proliferation and survival. STAT5A inhibition has been shown in vitro and in vivo to reduce the development of breast cancer cells. As a result, we have screened compounds from the FDA database that might serve as potential inhibitors of STAT5a through virtual screening, docking, DFT and MD simulation approaches. The drug Nilotinib has shown promising results inhibiting STAT5a. Further, in-vitro analysis will be carried forward to understand the anti-cancer activity.

• Molecules and Cells
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• 제23권1호
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• pp.94-99
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• 2007

Suppressors of cytokine signaling (SOCS) family members are negative feedback regulators of the Jak/Stat pathway, which is an essential inflammatory signaling pathway. We investigated expression of eight members of the SOCS family in rat astrocytes, using two inflammatory stimulants, PMA and IFN-${\gamma}$. Only a few SOCS genes were induced by both stimulants, and we detected an increase in SOCS5 protein with PMA. PMA activated the Jnk, Erk, p38, and Jak/Stat signal pathways. In addition, it increased the level of activated-Stat3 resulting from tyrosine phosphorylation. A gel-shift assay showed that a protein in nuclear extracts from PMA-treated cells was able to bind to Stat binding elements. These results suggest that activated Stat3 binds to SOCS promoters and leads to their transcriptional induction.

• 생명과학회지
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• 제9권1호
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• pp.50-57
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• 1999

STAT들은 다양한 cytokine이나 성장호르몬 등에 의해 활성화되어 핵으로 빠르게 이동되어 유전자 발현을 조절한다. 우리는 D-raf 유전자의 5' 발현조절영역에서 STAT결합부위 염기서열을 발견하였다. 본 연구는 D-raf 유전자발현조절에 있어서 STAT결합부위의 역할을 형질전환 초파리를 사용하여 조사하였다. STAT결합부위에 염기치환돌연변이를 도입시킨 D-raf promoter부분을 P인자 벡터의 IacZ유전자에 융합시킴으로써 리포터 플라스미드 pDraf-STATmut-lacZ를 제작하였다. 이 리포터 플라스미드를 이용하여 얻은 Draf-STATmut-lacZ형질전환 초파리의 lacZ발현을 발생단계별, 조직별로 조사한 결과, 거의 모든 발생단계에서 정상형 Draf-lacZ 형질전환 초파리의 lacZ발현에 비해 크게 감소하였다. 본 연구결과들은 STAT결합배열 부위가 D-raf유전자발현조절에 있어서 중요한 역할을 함을 개체수준에서 증명하고 있다.

• 통합자연과학논문집
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• 제16권3호
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• pp.81-95
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• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

• The Korean Journal of Physiology and Pharmacology
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• 제13권5호
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• pp.337-341
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• 2009

Signal transducer and activator of transcription 4 (STAT4), a STAT family member, mediates interleukin 12 (IL12) signal transduction. IL12 is known to be related to calorie-restricted status. In the central nervous system, IL12 also enhances the production of nitric oxide (NO), which regulates food intake. In this study, the expression of neuronal NO synthase (Nos1), which is also related to food intake, was investigated in the hypothalamic areas of Stat4 knockout (KO) mice using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry, a marker for neurons expressing Nos1 enzyme. Western blots were also performed to evaluate Nos1 and Fos expression. Wild-type Balb/c (WT group, n=10 male) and Stat4 KO mice (Stat4 KO group, n=8 male) were used. The body weight and daily food intake in the WT group were $22.4{\pm}0.3$ and 4.4 g per day, while those in the Stat4 KO group were $18.7{\pm}0.4$ and 1.8 g per day, respectively. Stat4 mice had lower body weight and food intake than Balb/c mice. Optical intensities of NADPH-d-positive neurons in the paraventricular nucleus (PVN) and lateral hypothalamic area (LHA) of the Stat4 KO group were significantly higher than those of the WT group. Western blotting analysis revealed that the hypothalamic Nos1 and Fos expression of the Stat4 KO group was up-regulated, compared to that in the WT group. These results suggest that Stat4 may be related to the regulation of food intake and expression of Nosl in the hypothalamus.

• 치위생과학회지
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• 제19권2호
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• pp.141-146
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• 2019

Background: Oral cancer has a high incidence worldwide and has been closely associated with smoking, alcohol, and infection by the human papillomavirus. Metastasis is highly important for oral cancer survival. Lysophosphatidic acid (LPA) is a bioactive lipid mediator that promotes various cellular processes, including cell survival, proliferation, metastasis, and invasion. Signal transducer and activator of transcription (STATs) are transcription factors that mediate gene expression. Among the seven types of STATs in mammals, STAT3 is involved in invasion and metastasis of numerous tumors. However, little is known about the role of STAT3 in oral tumor invasion. In the present study, we hypothesized that STAT3 mediates LPA-induced oral cancer invasion. Methods: Immunoblotting was performed to analyze LPA-induced STAT3 activation. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to assess the survival rates of YD-10B cells. STAT3 levels in LPA-treated oral tumor cells were evaluated by performing in vitro invasion assay. Results: To the best of our knowledge, this is the first study to demonstrate that LPA enhances STAT3 phosphorylation in oral cancer. In addition, treatment with WP1066, a selective inhibitor of STAT3, at a concentration that does not cause severe reduction in cell viability, significantly attenuated LPA-induced YD-10B cancer cell invasion. Conclusion: The results suggested that LPA induces oral tumor cells with greater invasive potential via STAT3 activation. Our findings provided important insights into the mechanisms underlying mouth neoplasms.

• 대한의용생체공학회:의공학회지
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• 제19권3호
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• pp.279-284
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• 1998

체온을 섭씨 20도 이하로 인위적으로 감소시켜 혈액 순환을 일시적으로 중단시키는 초저체온 순환정지법은 심장수술의 한 보조방법으로 유용하게 이용되고 있다. 이러한 초저체온 상태는 정상적인 생리 상황이 아니기 때문에 이때 두가지 저체온 혈액가스 조절법인 STAT와 pH-STAT 조절법 중 어느 쪽을 택하는 것이 좋으냐에는 이론이 많다. 본실험은 막형 산화기를 사용한 심폐바이패스 생체 실험회로에서 두 저체온 혈액가스 조절법의 기술적인 측면을 비교하는데 목적이 있다. 실험동물로는 모두 14마리의 어린 돼지를 사용하였는데 두 실험군에 7마리씩 배정하였다. 정중흉골절개술후 동정맥 캐뉼라를 삽관하고 심폐바이패스를 시행하였다. 2500 ml/min의 관류 속도하에서 비인두 체온으로 2$0^{\circ}C$까지 관류냉각을 시행하고 40분 동안 초저체온 순환정지를 시행하였다. 냉각기간 동안 실험군에 따라 STAT 또는 pH-STAT군의 22.83$\pm$2.14분 보다 유의하게 짧았으나, 재가온시간에서는 STAT군(40.0$\pm$5.07분)과 pH-STAT군(46.5$\pm$6.32) 사이에 유의한 차이는 없었다. PH-STAT에서는 3.0-5.5 % 사이의 이산화탄소가 주입되었고 STAT에서는 이산화탄소의 추가 투여가 없었다. 산소 투여는 체온 감소와 함께 점진적으로 감소시켰다. 두 실험군 모두에서 PH, 이산화탄소분압 및 산소분압이 만족스럽게 조절되었다.

• Journal of Chest Surgery
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• 제31권6호
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• pp.553-559
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• 1998

서론: 초저체온 순환정지법은 일부 심장수술에서 매우 유용하게 사용되고 있다. 그러나 사람은 정상 생리상태에서 이 정도 저체온에 노출되는 적이 없기 때문에 초저체온 상태에서 $\alpha$-STAT와 pH-STAT 산-염기 조절법 중 어느 쪽을 택하는 것이 좋으냐에는 여전히 이론이 많다. 본실험에서는 어린 돼지에서 초저체온 순환정지 실험모델을 확립한뒤 pH-STAT와 $\alpha$-STAT 간에 (1) 심폐바이패스 냉각 및 재가온시 뇌냉각 및 재가온 속도 비교, (2) 뇌혈류, 뇌대사 및 뇌혈류/뇌대사 비의 변화 양상 분석, 그리고 (3) 초저체온 순환정지후 뇌부종 정도를 비교 분석하였다. 대상 및 방법: 25~30 KG의 어린 돼지를 실험군마다 7마리씩 사용하였다. 마취후 두개골을 절제하고 상시상동 삽관을 통해 뇌혈류를 측정하였다. 그리고 정중흉골절개술 및 캐뉼라 삽관후 심폐바이패스를 시행하였다. 막형 산화기와 롤러펌프를 사용하였고, 관류속도는 2500 ml/min로 유지시켰다. 심폐바이패스 시작후 첫 10~15분 동안 정상체온 관류를 시행한 뒤 이어 $20^{\circ}C$(비인두체온) 까지 관류냉각을 시행하였다. $20^{\circ}C$에서 40분 동안 완전순환정지를 시행하였다. 냉각기간 동안 실험군에 따라 $\alpha$-STAT 또는 pH-STAT에 따른 산-염기 조절을 시행하였다. 순환정지후에는 정상 체온까지 재가온하였다. 재가온 종료후 실험동물을 희생시키고 뇌를 추출하였다. 뇌혈류 및 뇌대사 측정은 바이패스전, 냉각전, 순환정지전, 재가온후 15분, 재가온 종료시, 재가온 종료후 1시간에 각각 시행하였다. 결과: 양군간 냉각시간은 $\alpha$-STAT군이 16.57$\pm$5.13분으로 pH-STAT 군의 22.83$\pm$2.14분 보다 유의하게 짧았으나(P<0.05), 재가온시간에서는 $\alpha$-STAT군(40.0$\pm$5.07분)과 pH-STAT군(46.5$\pm$6.32) 사이에 유의한 차이는 없었다. 뇌혈류 및 뇌대사에서는 pH-STAT군이 $\alpha$-STAT군에 비하여 높은 경향을 보였지만 통계학적으로 유의한 차이는 없었다. 뇌혈류량/뇌대사율의 비에서도 두군간에 차이가 없었다. 그러나 두 실험군내에서 체온변화에 따른 뇌혈류량 및 뇌대사의 차이는 유의하였다. 특히 비인두체온 20도에서는 뇌대사율의 감소가 뇌혈류의 감소 보다 더욱 커서 결과적으로 뇌혈류량/뇌대사율의 비는 1 보다 높은 수치로 기록되었다. 뇌수분양은 두 실험군간에 유의한 차이는 없었다. 결론: 본 실험에서 $\alpha$-stat와 pH-STAT 산염기 조절법간에 냉각시간 이외에는 유의한 차이가 없음을 알 수 있었다.

• BMB Reports
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• 제34권5호
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• pp.484-488
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• 2001

STATs are proteins with a dual function: signal transducers in the cytoplasm and transcriptional activators in the nucleus. Among the six known major STATs (STAT1-6), STAT3 has been implicated in the widest range of signaling pathways that regulate cell growth and differentiation. As a part of our on-going investigation on the pleiotropic functions of STAT proteins, we examined the role of STAT3 as a molecular adaptor that links diverse cell growth signaling pathways. We observed that STAT3 can be specifically activated by multiple cytokines, such as IL-3, in transformed fibroblasts and IL-4 or IFN-$\gamma$ in primary immune cells, respectively. The selective activation of STAT3 in H-ras-transformed NIH3T3 cells is associated with an increased expression of phosphoserioe STAT3 in these cells, compared to the parental cells. Notably phosphoresine-STAT3 interacts with oncogenic ras, shown by immunoprecipitation and Western blots. The results suggest the role of STAT3 in rasinduced cellular transformation as a molecular adaptor linking the Jak/STAT and Ras/MAPK pathways. In primary immune cells, IL-4 and IFN-$\gamma$ each induced (in addition to the characteristic STAT6 and STAT1 homodimers) the formation of STAT3-containing complexes that bind to GAS probes, which correspond to the $Fe{\varepsilon}$ Rll and $Fe{\gamma}$ RI promoter sequences, respectively. Since IL-4 and IFN-$\gamma$ are known to counter-regulate the expression of these genes, the ability of STAT3 to form heterodimeric complexes with STAT6 or STAT1 implies its role in the fine-tuned control of genes that are regulated by IL-4 and IFN-$\gamma$.