B-RafV600E에 의한 갑상샘 발암과정에서 Thyroid stimulating hormone (TSH) 의 역할연구

I. INTRODUCTION 1 II. MATERIALS AND METHODS 4 1. Tumor Samples from Patients 4 2. Cloning of B-RafV600E, DUSP6, and c-Myc and Lentivirus Preparation 4 3. Isolation and Culture of Thyrocytes 4 4. Immunohistochemistry and Immunocytochemistry 5 5. Immunoblotiitng 5 6. Analysis of B-RafV600E Mutation 6 7. Immunoprecipitation-Phosphatase Activity Assay 6 8. Measurement of Ras Activity 7 9. Real-Time PCR Analysis 7 10. Measurement of Reactive Oxygen Species 8 11. RNA Interference 8 12. Senescence-Associated β-Galactosidase Staining 9 13. Analysis of DUSP6 Protein Stability 9 14. Migration assay 9 15. Invasion assay 9 16. 3D gel invasion assay 10 17. Statistical Analysis 10 III. RESULTS 11 1. B-RafV600E Induces OIS in Primary Thyrocytes. 11 2. Cancer Cells in B-RafV600E PTC Tissues Escape from OIS. 14 3. TSH Increases DUSP6 Expression through Regulation of ROS Generation. 20 4. TSH Signaling Inhibits B-RafV600E–Induced Senescence through DUSP6. 28 5. Ras/AKT/c-Myc Signaling Is Reactivated by TSH and DUS6. 34 6. Senescent cells in the invasive regions of B-RafV600E-induced PTC tissues. 42 7. B-RafV600E-induced senescent cells expressed SASP especially MMPs. 48 8. Cell invasion was dependent on OIS. 53 9. Cells with a senescent phenotype were found in regional LNs and the lymphatic channel. 55 10. Senescent cells mediate cancer cell invasion by means of the CXCR4 and CXCL12 interaction. 57 11. CXCR4 expression is correlated with CXCL12 level and invasion ability. 62 IV. DISCUSSION 70 V. CONCLUSION 79 VI. REFERENCES 80 국문요약 88

Author dc:creator

• 김, 영화

Contributors dc:contributor

• 대학원 의생명과학과
• 108365

• B-RafV600E
• TSH
• DUSP6
• ROS
• MMPs
• CXCR4
• CXCL12
• Papillary thyroid carcinogenesis

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000021821
000000021821

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/13014