• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.117-129
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• 2000

This study was carried out to examine proliferative activity and expression of c-myc oncoprotein and p2lras in normal and preneoplastic rat livers induced by an in vivo mid-term chemical carcinogenesis assay. Sixty, six-week-old male specific pathogen free Sprague-Dawley male rats were randomly divided into five groups. Group I was received a single intraperitoneal(IP) dose(200mg/kg) of diethylnitrosamine(DEN). Group 2(10 rats) was operated partial hepatectomy(PH) and Group 3 was received IP(200mg/kg) DEN, fed two weeks later with 500ppm of phenobarbital(PB). Group 4 was received IP(200mg/kg) DEN, fed two weeks later 500ppm(PB) and PH at week 3 after the onset of experiment. While group 5(20 rats) was not treated and used as a control group. All the rats were sacrificed at age 14 weeks except 10 rats from group 5 were sacrificed at the onset of experiment. Livers of all rats were examined for 5-bromo-2'-deoxyuridine(BrdU) incoporation, proliferating cell nuclear antigen(PCNA), silver-binding nucleolar organizer regions(AgNORs) counts per nucleus and expression of c-myc oncoprotein and p21ras. Both the number and area of the preneoplastic lesions were significantly(p<0.01) compared to other groups. A significant(p<0.01) increase in immunoreactive cells were detected in preneoplastic hepatocytes in Groups 3 and 4 by PCNA and BrdU immunohistochemical stain. The number of the positive cells were significantly(p<0.05) lower in normal 14-week-old rats than those of 6-week-old rats. The results showed that proliferative activity of the hepatocytes was increased by treatment with DEN, PH and PB. Meanwhile, AgNORs counts per nucleus were significantly(p<0.05) increased in the preneoplastic hepatocytes of rats in both groups 3 and 4. The expression of c-myc oncoprotein and p21ras were more readily localized within the hepatic preneoplastic lesions such as hyperplastic nodules. Especially, group 4 showed significantly (p<0.05) overexpressed levels compared to groups 1 and 3. These findings suggest that PCNA, BrdU and AgNORs are significantly increased and c-myc oncoprotein and p21ras are significantly overexpressed in hepatic preneoplastic lesions induced by mid-term carcinogenesis. So these parameters can be an effective markers for hepatic prencoplastic lesions.

• Genomics & Informatics
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• v.13 no.2
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• pp.60-67
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• 2015

The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.760-761
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• 2005

• Proceedings of the Microbiological Society of Korea Conference
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• 2009.05a
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• pp.98-98
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• 2009

• BMB Reports
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• v.34 no.1
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• pp.80-84
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• 2001

The human papillomavirus E7 protein can form a specific complex with a retinoblastoma tumor suppressor gene product (p105-Rb) that results in the release of the E2F transcription factor, which is critical for the growth-deregulation and transforming properties of the viral E7 oncoprotein. In an attempt to apply interaction between the E7 oncoprotein and a target cellular protein Rb for an in vitro screening system for drugs against human papillomavirus infection, we primarily investigated the E7Rb binding through a pull down assay and enzyme-linked immunosorbent assay. The pull down assay showed that both glutathione S-transferase-tagged E7 and His-tagged E7 immobilized on resins specifically produced complexes with bacterially expressed Rb in a dose-dependent manner, as determined by immunoblot analyses. This result coincided with that of an enzyme-linked immunosorbent assay, which is a useful system for the mass screening of potential drugs. Taken together, this screening system (based on the interaction between E7 and Rb) can be a promising system in the development of drugs against cervical cancers caused by human papillomavirus infection.

• Journal of Chest Surgery
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• v.33 no.1
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• pp.60-67
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• 2000

Background: Microsatellites are short-tandem repeated uncleotide sequences present throughout the human genome. Alterations of microsatellites have been termed microsatellite instability(MI). It has been generally known that microsatellite instability detected in hereditary non-polyposis colorectal cancer (HNPCC) reflects genetic instability that is caused by impairments of DNA mismatch repair system regarding as a novel tumorigenic mechanism. A number of studies reported that MI occurred at varying frequencies in non-small cell lung carcinoma (NSCLC). However It has been unproven whether MI could be a useful market of genetic instability and have a clinical significance in NSCLC. Material and Method : We have examined whether MI can be observed in thirty NCSLC using polymerase chain reaction whether such alterations are associated with other molecular changes such as p53, K-ras and c-myc oncoproteins expression detected by immunohistochemical stain,. Result: MI(+) was observed in 16.6%(5/30) and MI(-) was 83.3% (25/30) Average age was 50$\pm$7.5 year-old in MI(+) group and 57$\pm$6.6 year-old in MI(-) group. Two year survival rate in MI(=) group (20% 1/5) was worse than MI(-) group (64% 16/25) with a statistic difference. (P=0.04) The positive rate of K-ras oncoprotein expression and simultaneous expression of 2 or 3 oncoproteins expression were higher in MI(+) group than MI(-) group with a statistic difference(P=0.05, P=0.01) Conclusion: From, these results the authors can conclude that MI is found in some NSCLC and it may be a novel tumorigenic mechanism in some NSCLC. We also conclude that MI could be used as another poor prognostic factor in NSCLS.

• Korean Journal of Pharmacognosy
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• v.35 no.4 s.139
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• pp.368-374
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• 2004

Cervical cancer is one of the leading causes of female death. Viral oncoproteins E6 and E7 are selectively retained and expressed in carcinoma cells infected with HPV (Human papillomavirus) type 16. The HPV is cooperated in immotalization and transformation of primary keratinocyte. E6 and E7 oncoproteins interfere the functions of tumor suppressor proteins p53 and retinoblasoma protein (pRb), respectively. Among a lots of natural products, Artemisia scoparia Waldstein et Kitamura has inhibitory effects on the binding between E6 oncoprotein and tumor suppressor p53, or the binding between E6 and E6 associated protein (E6AP), an E3 ubiquitin-protein ligase. HPV oncoprotein inhibitors from Artemisia scoparia W. were isolated by solvent partition and column chromatography (Silica gel, RP-18) and the inhibitory compounds were finally purified by HPLC using an ELISA screening system based on the binding between E6 and E6AP. The aim of this study is to identify the structure of inhibitory compounds and to investigate whether these compounds have inhibitory effects on the functions of E6 oncoprotein. We investigated whether 3,5-di-O-caffeoylquinic acid (DCQA) extracted from Artemisia scoparia W. Could inhibit the function of E6 oncoprutein. DCQA inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53 and also inhibited the proliferation of human cervical cancer cell lines (SiHa and CaSKi) in a dose response manner. These results suggest that DCQA inhibited the function of E6 oncoprotein, suggesting that it can be used as a potential drug for the treatment of cervical cancers infected with HPV.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.79-95
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• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• BMB Reports
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• v.38 no.2
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• pp.243-247
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• 2005

Dishevelled (Dvl) is a positive regulator of the canonical Wnt signaling pathway, which regulates the levels of $\beta$-catenin. The $\beta$-catenin oncoprotein depends upon the association of Dvl and Axin proteins through their DIX domains, and its accumulation directs the expression of specific developmental-related genes at the nucleus. Here, the $^1H$, $^{13}C$, and $^{15}N$ resonances of the human Dishevelled 2 DIX domain are assigned using heteronuclear nuclear magnetic resonance (NMR) spectroscopy. In addition, helical and extended elements are identified based on the NMR data. The results establish a structural context for characterizing the actin and phospholipid interactions and binding sites of this novel domain, and provide insights into its role in protein localization to stress fibers and cytoplasmic vesicles during Wnt signaling.

• BMB Reports
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• v.45 no.12
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• pp.719-723
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• 2012

A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ~30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy.