STAT3 Stabilizes C/EBPβ in H-Ras Transformed Mammary Epithelial Cells
인체유방상피세포에서 STAT3에의한 C/EBPβ 안정화
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 약학과, 2015. 2. 서영준.
- STAT3 (Signal transducer and activator of transcription 3) plays important roles in cancer-related inflammation by controlling expression of pro-inflammatory cytokines and chemokines. Recent studies suggest STAT3 and C/EBPβ (CCAAT-enhancer binding protein beta) synergistically increase cancer cell proliferation and epithelial-mesenchyml transition (EMT) in breast and brain cancer respectively. C/EBPβ is a leucine-zipper transcription factor that regulates expression of a variety of inflammatory cytokines or chemokines, such as IL-8, G-CSF (granulocyte colony stimulating factor), and GM-CSF (granulocyte macrophage colony stimulating factor) which induce neutrophil infiltration and differentiation. However, the molecular mechanism by which STAT3 and C/EBPβ cooperatively interact has not been fully elucidated. In this study, I found that the level of C/EBPβ protein but not that of its mRNA transcript was decreased in the absence of STAT3 in H-Ras MCF10A cells. In addition, silencing STAT3 dramatically induced proteasomal degradation of C/EBPβ and thus suppressed transcription of C/EBPβ target genes. Furthermore, direct interaction between STAT3 and C/EBPβ was confirmed by immuno-precipitation. Taken together, STAT3 stabilizes C/EBPβ thereby promoting cancer-associated inflammation.