유방의 양성 및 악성병변의 ras Oncogene표현에 관한 연구

남종희,이종현,박창수,조규혁 대한병리학회 1989 Journal of Pathology and Translational Medicine Vol.23 No.1

성장호르몬 분비성 뇌하수체 선종에서 소마토스타틴 수용체 (제2아형, 제5아형), G_i2α 및 Pit-1 유전자 발현

류미숙,양인명,박철영,우정택,김성운,김진우,김영설,최영길,김은희,박승준,김국기 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.2

Background: Mutation of Gs protein subunit (gsp oncogene), detected in about 30∼40% of growth hormone (GH)-secreting pituitary tumors, is associated with an increased long-acting somatostatin analog octreotide sensitivity. However, the mRNA expression of somatostatin receptor (sst) was not changed in the GH-secreting pituitary tumor, regardless of whether they were gsp oncogene positive or negative. This suggests that the expression of genes coding for G_i2α, Pit-1 and the other factors involved in the regulation of secretory activity in somatotrophs is likely to be altered in gsp oncogene positive tumors. We observed the impact of the gsp oncogene on the expression of the genes coding for Gi2, Pit-1 and sst (2&5) in GH-secreting pituitary tumors. Methods: The GH response to octreotide was examined in 13 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were extracted from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gs gene. Sst2, sst5, G_i2α and Pit-1 mRNA levels were measured by semi-quantitative RT-PCR. Results: Sst2 and sst5 mRNA transcripts were detected in all tumors (7 gsp +, 6 gsp-). The amount of sst transcripts varied considerably varied between the tumors. There were no significant differences in sex, age, tumor size, grade or basal GH levels. Pit-1 and sst2 mRNA levels were not different. In contrast, G_i2 mRNA levels were significantly higher in gsp (+) while sst5 mRNA levels were higher in gsp (-). Conclusion: These data suggests that gsp oncogene may increase Gi2α levels but decrease sst5 mRNA levels. However, Pit-1 and sst2 mRNA expression may not be affected by gsp oncogene. The increased expression of the G_i2α gene might be an inhibitory compensatory response to the action of gsp oncogene

표피 중상 세포의 ras Oncogene 표현에 관한 연구

김성균(Sung Kyun Kim),최규철(Kyu Chul Choi),황선욱(Sun Wook Hwang) 대한피부과학회 1988 大韓皮膚科學會誌 Vol.26 No.2

DNA isolated from human tumor cells can induce malignant transfarmation of tissue culture cells. The DNA is then called an oncogene. Its protein produets have been detected in animal and human tumors and are considered to play a significant role in carcinogenesis. In order to evaluate whether the oncogenes are involved in development of tumors of epidermis and whether they could be used as tumor markers, immunoperoxidase staining was performed for the ras product in sections of squamous cell carcinoma, Bowen's disease, actinic keratosis, keratoacanthoma and seborrheic keratosis. Three cases of sgamous cell carcinoma showed 10~20 positive cells per high power field(HPF). Three cases of Bowen's disease revealed 1-9 positive cells per HPF, whereas the actinic keratosis 1~9 or no positive cells per 10 HPF in all three cases. The keratoacanthoma and seborrheic keratosis showed 1~9 or no positive cells in all observed cases. The positive staining was observed in the cytoplasm. The increasing positivity in parallel with the increase of malignant potential strongly suggests that the ras oncogene is closely related to development of epidermal malignancy and also point out the possibility of ras as a cancer marker.

Basic, Research : Rapid Induction of Liver Cancer using Hydrodynamic Transfection of Oncogene-encoding Plasmids

( Hye Lim Ju ),( Sang Hoon Ahn ),( Do Young Kim ),( Sinhwa Baek ),( Sook In Chung ),( Kwang Hyub Han ),( Simon Weonsang Ro ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background : Liver cancer is a complex multistep process requiring genetic alterations in multiple proto-oncogenes and tumor suppressor genes. Although hundreds of genes are known to play roles in hepatocarcinogenesis, oncogenic collaboration among these genes is still largely unknown. We developed various non-germline transgenic mouse models using hydrodynamics- based transfection and the Sleeping Beauty transposon system. Here, we report a method by which oncogenic collaboration of various cancer-related genes in the liver can be easily investigated in vivo by bioluminescence imaging (BLI) of tumors. Methods: Transposon vectors each encoding an oncogene or down-regulating a tumor suppressor gene (HrasG12V, SmoM2, and shp53) were constructed. To induce liver cancer, total 50 μg of the three plasmids-encoding the Sleeping Beauty transposase and two transposons-were diluted in 2.5 mL of 0.9% saline and then injected into the lateral tail veins of male 5- to 6-week-old C57BL/6 mice. Tumors were observed via BLI. Results: Very strong BLI signals were observed at 4 weeks post-hydrodynamic injection (PHI) in mice co-expressing HrasG12V and shp53, while only background signals were detected in other double or single transgenic groups until 30 weeks PHI. Consistent with the BLI data, tumors were observed in the HrasG12V plus shp53 group at 4 weeks PHI, while other transgenic groups failed to exhibit a hyperplastic nodule at 30 weeks PHI. Conclusion: The methodology described here is expected to accelerate and facilitate in vivo studies of the hepatocarcino genic potential of cancer-related genes by means of oncogenic cooperation.

N-ras Oncogene에 의해 면형된 NIH 3T3 Cell에서의 포도당 흡수변화

한동표,최종환 연세대학교 원주의과대학 1995 원주의대논문집 Vol.8 No.1

생쥐에서 종양세포의 암유전자발현에 대한 울솔산의 효과

류태형(Tae Hyong Rhew),박성미(Sung Mi Park),박건영(Kun Young Park),정해영(Hae Young Chung),하재청(Jae Chung Hah),이정규(Chung Kyu Lee) 대한약학회 1992 약학회지 Vol.36 No.6

To investigate the effect of ursolic acid on the expression of oncogenes in tumor cells of mice, sarcoma 180 ascites tumor cells were implanted into the left groin of ICR mice and the tumor bearing mice were treated with ursolic acid. The expression of oncogenes were measured by in situ hybridization method. Ursolic acid significantly reduced the expression of oncogenes in the tumor cells. Therefore, it can be said that the prestated anticarcinogenic effect of ursolic acid could be partly ascribed to the mechanism included in the oncogene''s transcription level.

자궁경부암에서 인유두종 바이러스 핵산의 검출과 암유전자 c-myc과 Ha-ras 발현에 대한 연구

최호선(HS Choi),변지수(JS Pyun),박창수(CS Park) 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.12

The aim of the study was to investigate the role of human papillomavirus(HPV) and c-myc and Ha-ras oncogenes in carcinoma in situ and invasive cervical carcinoma. The presence of high-risk HPV(16/18, 31/33/35) DNA and expression of c-myc and c-Ha-ras oncogenes were studied in paraffin-embedded specimens obtained from 312 patients by using in situ hybridization and immunohistochemisty. Of 116 patients with carcinoma in situ, c-myc and Ha-ras expression was found in 14(37.8%) and 17(45.9%) patients with HPV DNA compared to 16(20.3%) and 19(24.4%) without HPV DNA(P<0.05). Of 196 patients with invasive squamous cell carcinoma, c-myc and Ha-ras expression was found in 21(27.6%) and 30(39.5%) patients with HPV DNA, 36(30%) and 48(40%) without HPV DNA. Ha-ras oncogene was detected in 24.4% of patients with carcinoma in situ while in 40% of invasive squamous cell carcinoma without HPV DNA(P<0.05). Our results suggest that c-myc and Ha-ras oncogenes` expression and HPV infection could play a role in the carcinogenesis of invasive squamous cell carcinoma of the cervix.

TSH Signaling Overcomes B-RafV600E–Induced Senescence in Papillary Thyroid Carcinogenesis through Regulation of DUSP6 ¹ ²

Kim, Young Hwa,Choi, Yong Won,Han, Jae Ho,Lee, Jeonghun,Soh, Euy Young,Park, So Hyun,Kim, Jang-Hee,Park, Tae Jun Neoplasia Press 2014 Neoplasia Vol.16 No.12

<P>B-RafV600E oncogene mutation occurs most commonly in papillary thyroid carcinoma (PTC) and is associated with tumor initiation. However, a genetic modification by B-RafV600E in thyrocytes results in oncogene-induced senescence (OIS). In the present study, we explored the factors involved in the senescence overcome program in PTC. First of all, we observed down-regulation of p-extracellular signal-regulated kinases 1/2 and up-regulation of dual specific phosphatase 6 (DUSP6) in the PTC with B-RafV600E mutation. DUSP6 overexpression <I>in vitro</I> induced extracellular signal-regulated kinases 1/2 dephosphorylation and inhibited B-RafV600E–induced senescence in thyrocytes. Although DUSP6 protein was degraded by B-RafV600E–induced reactive oxygen species (ROS), thyroid-stimulating hormone (TSH) stabilized DUSP6 protein by increasing Mn superoxide dismutase expression and inhibited B-RafV600E–induced senescence. Although serum TSH was not increased, its receptor was markedly upregulated in PTC with B-RafV600E. Furthermore, TSH together with DUSP6 reactivated Ras signaling, resulted in activation of Ras/AKT/glycogen synthase kinase 3β, and stabilized c-Myc protein by inhibiting its degradation. These observations led us to conclude that increased TSH signaling overcomes OIS and is essential for B-RafV600E–induced papillary thyroid carcinogenesis.</P>

급성백혈병에서 염색체 이상과 암유전자의 전좌

장성익,양창헌 啓明大學校 醫科大學 1993 계명의대학술지 Vol.12 No.3

To investigate the specific chromosomal abnormalities and role on oncogenes in human acute leukemia, bone marrow cells from ten cases of acute leukemia patients were cultured and karyotyped after G-banding. DNA in situ hybridization was also performed on the same samples with K-ras, erb-B2, mos and p53 oncogenes. The most characteristics of chromosome abnormalities were marker chromosomes, deletion types of (1)(q26), (2)(p25), (7)(q25), 8(q26), (16)(q24) and t(3;10)(q12;q11) in AML, while deletion types of (1)(q28), (1)(p11), (9)(q34) and t(9;22)(q34;q12) were found in ALL. It was found that three oncogenes (erb-B2, mos, p53) except K-ras were activated with translocation in both subtype leukemia by DNA in situ hybridization. It was obscure that chromosome aberrations and activation of oncogenes were not corelated by individuals. It is presumed that acute leukemia-related antioncogenes are located on the chromosome 1 and 2 and direct activating gene causing acute leukemia in oncogenesis is located on the chromosome 9. An activation of erb-B2, mos and p53 is related to the secondary effect on oncogenesis in acute leukemia.

Contributed Mini Review : Naturally occurring reoviruses for human cancer therapy

( Manbok Kim ) 생화학분자생물학회 2015 BMB Reports Vol.48 No.8

Naturally occurring reoviruses are live replication-proficient viruses that specifically infect human cancer cells while sparing their normal counterpart. Since the discovery of reoviruses in 1950s, they have shown various degrees of safety and efficacy in pre-clinical or clinical applications for human anti-cancer therapeutics. I have recently discovered that cellular tumor suppressor genes are also important in determining reoviral tropism. Carcinogenesis is a multi-step process involving the accumulation of both oncogene and tumor suppressor gene abnormalities. Reoviruses can exploit abnormal cellular tumor suppressor signaling for their oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ataxia telangiectasia mutated (ATM), and retinoblastoma associated (RB) are known to play important roles in genomic fidelity/maintenance. Thus, a tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to the accumulation of genetic defects which in turn could result in oncolytic reovirus susceptibility. This review outlines the discovery of oncolytic reovirus strains, recent progresses in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and reoviral oncotropism, and their clinical implications. Future directions in the utility of reovirus virotherapy is also proposed in this review. [BMB Reports 2015; 48(8): 454-460]