• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.107-107
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• 2003

The activation of protooncogenes or the inactivation of their gene products may be a specific and effective functional study for human neoplasia. To examine this possibility, we have used the tetracycline regulatory system to generate transgenic mice that conditionally express the HccR-2 protooncogene in vivo. The new human cervical cancer protooncogene (HccR-2) was detected from cervical cancer cell line. To elucidate its biological functions, we generated transgenic mice that expressed the HccR-2 gene. The sustained expression of the HccR-2 transgene culminated chronic neutrophilic leukemia (CNL). CNL is a rare chronic myeloproliferative disorder that presents as a sustained, mature neutrophilic leukocytosis with few or no circulating immature granulocytes, the absence of peripheral blood monocytosis, basophilia, or eosinophilia, and infiltration of neutrophils at the liver, spleen and kidney. Mice expressing the HccR-2 and tetracycline-transactivating protein (tTa) transgene were found to have altered myeloid development that was characterized by increased percentages of mature neutrophil and band form neutrophil in the peripheral blood, liver and spleen. Activation of the transgene causes CNL. In our model, expression of HccR-2 transgene mice was similar in many respects to the human CNL. This model will be valuable not only for investigating the biological properties of the HccR-2 and other protooncogenes in vivo but also for analyzing the mechanism involved in the progression of CNL.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.819-825
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• 2003

pharbitis nil and Taraxacum mongolicum are representative herbs that have been used for cancer treatment in Korean traditional medicine. To understand the molecular basis of the antitumor function, we analyzed the effect of these herbs on proliferation and apoptosis of tumor cells using a gastric cancer cell line AGS. Cell counting assay showed that pharbitis nil strongly inhibit cell proliferation Of AGS whereas Taraxacum mongolicum exhibit no detectable effect on cellular growth. [³H]thymidine uptake analysis also demonstrated that DNA replication of AGS is suppressed in a dose-dependent manner by treatment with pharbitis nil. Additionally, tryphan blue exclusion assay showed that Pharbitis nil induce apoptotic cell death of AGS in a dose-dependent. To explore whether anti antiproliferative and/or proapototic property of Pharbitis nil is associated with their effect on gene expression, we performed RT-PCR analysis of cell cycle- and apoptosis-related genes. Interestingly, mRNA expression levels of c-Jun, c-Fos, c-Myc, and Cyclin D1 were markedly reduced by Pharbitis nil. Taraxacum mongolicum also showed inhibitory action on expression of these growth-promoting protooncogene but there effects are less significant, as compared to Pharbitis nil. Furthermore, it was also found that Pharbitis nil activates expression of the p53 tumor suppressor and its downstream effector p21Waf1, which induce G1 cell cycle arrest and apoptosis. Collectively, our data demonstrate that Pharbitis nil induce growth inhibition and apoptosis of human gastric cancer cells and these effects are accompanied with down-and up-regulation of growth-regulating protooncogenes and tumor suppressor genes, respectively. This observation thus suggests that the anticancer effect of Pharbitis nil might be associated with its regulatory capability of tumor-related gene expression.

• Reproductive and Developmental Biology
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• v.35 no.4
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• pp.421-425
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• 2011

The experimental manipulation of protooncogenes and their gene products is a valuable research tool for the study of human neoplasia. In this study, the recently identified human cervical cancer protooncogene (HccR-2) was expressed in transgenic mice under the control of the tetracycline regulatory system. The phenotype observed was similar in many respects to human chronic neutrophilic leukemia (CNL). Thus, the HccR-2 transgenic mouse model is important not only for investigating the biological properties of the HccR-2 protooncogene in vivo, but also for analyzing the mechanisms involved in the progression of CNL.

• Reproductive and Developmental Biology
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• v.35 no.4
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• pp.415-420
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• 2011

The experimental manipulation of protooncogenes and their gene products is a valuable research tool for the study of human neoplasia. In this study, the recently identified human cervical cancer protooncogene (HccR-2) was expressed in transgenic mice under the control of the tetracycline regulatory system. Mice expressing the HccR-2 transgene showed an altered myeloid development characterized by an increased percentage of mature and band-form neutrophils in the peripheral blood, liver and spleen. This phenotype is similar to human chronic neutrophilic leukemia (CNL) in many ways, which is a rare chronic myeloproliferative disorder (CMD) that presents as a sustained leukocytosis of mature neutrophils with a few or no circulating immature granulocytes, an absence of peripheral blood monocytosis, basophilia, or eosinophilia, and an infiltration of neutrophils into the liver, spleen and kidney. Thus, the HccR-2 transgenic mouse model is imperative not only for investigating the biological properties of the HccR-2 protooncogene in vivo, but also for analyzing the mechanisms involved in the progression of CNL.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.54-54
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• 2003

The activation of protooncogenes or the inactivation of their gene products may be a specific and effective functional study for human neoplasia. To examine this possibility, we have used the tetracycline regulatory system to generate transgenic mice that conditionally express the HccR-2 protooncogene in vivo. The new human cervical cancer protooncogene (HccR-2) was detected from cervical cancer cell line. To elucidate its biological functions, we generated transgenic mice that expressed the HccR-2 gene. The sustained expression of the HccR-2 transgene culminated chronic neutrophilic leukemia (CNL). CNL is a rare chronic myeloproliferative disorder that presents as a sustained, mature neutrophilic leukocytosis with few or no circulating immature granulocytes, the absence of peripheral blood monocytosis, basophilia, or eosinophilia, and infiltration of neutrophils at the liver, spleen and kidney. Mice expressing the HccR-2 and tetracycline-transactivating protein (tTa) transgene were found to have altered myeloid development that was characterized by increased percentages of mature neutrophil and band form neutrophil in the peripheral blood, liver and spleen. Activation of the transgene causes CNL. In our model, expression of HccR-2 transgene mice was similar in many respects to the human CNL. This model will be valuable not only for investigating the biological properties of the HccR-2 and other protooncogenes in vivo but also for analyzing the mechanism involved in the progression of CNL.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.134-143
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• 2003

Objectives : We performed this study to understand the molecular basis of the antitumor effect of Saussurea lappa, Pharbitis nil, Plantago asiatica and Taraxacum mongolicum, which have been used for cancer treatment in Korean traditional medicine. Design: We analyzed, the effect of these medicinal herbs on proliferation and apoptosis of tumor cells and its association with gene expression, We performed semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) analysis of cell cycle- and apoptosis-related genes using a gastric cancer cell line AGS. Results : Cell counting assay and $[^3H]thymidine$ uptake analysis showed that Saussurea lappa and Pharbitis nil strongly inhibit cell proliferation of AGS in a dose-dependent manner. Interestingly, gene espression assay revealed that mRNA espression levels of c-Jun, c-Fos, c-Myc, and Cyclin D1 were markedly decreased by Saussurea lappa and Pharbitis nil. Furthermore, Saussurea lappa was identified to activate expression of the p53 tumor suppressor and its downstream effector $p21^{Wafl}$, which leads to $G_1$ cell cycle arrest and apoptosis. These observations suggest that the anticancer effect of Saussurea lappa and Pharbitis nil might be associated with their regulatory capability of tumor-related gene expression.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.653-658
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• 1993

Background: Recent advancement of molecular genetics has revealed that malignant transformation of a cell may be a complex multistep process and this process is grouped, in general, into two distinct categories, activation of protooncogenes and inactivation of tumor suppressor genes. This study was focused on the mutation of p53 tumor suppressor gene, because p53 gene mutation is now generally accepted to be one of the most frequent genetic changes in a variety of human cancers. Although lung cancer is one of the common cancers in Korea, the genetic change in the carcinogenesis process is not yet known clearly. To investigate the role of p53 gene mutation in lung cancer, we examined the mutations of exon 4-8 of the p53 gene in humna lung cancer cell lines, because most of the mutations of p53 gene have been reported to develop in exon 4-8. Method: Genomic DNA was obtained by the digestion of proteinase K and the extraction by phenol-chloroform-ethanol method from two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and one human small cell lung cancer cell line, H69. To detect the mutations of exon 4-8 of the p53 gene, polymerase chain reaction single-strand conformation polymorphism(PCR-SSCP) analysis was performed with the DNA extracted from the cells. Results: The mutation of p53 gene was present in all three cell lines tested. In PC-9, PC-14 and H69, the altered mobility was detected in exon 7, 7 and 5, respectively. Conclusion: These results suggest that p53 gene mutation plays an important role in certain steps of the carcinogenesis of human non-small cell and small cell lung cancer.