Research on visual expressions of Being Together through Finding Hidden Pictures : focused on my works

학위논문(석사)--서울대학교 대학원 :동양화과 동양화전문,2007.Maste

miR-622 inhibits the tumorigenesis of glioblastoma through GLUT3 repression

Histone deacetylases (HDAC) is modified histone-proteins. HDAC2 is a member of classⅠ HDAC and associated brain development. HDAC2 is highly expressed in various cancers and correlated with GBM progression. HDAC inhibitor is known to be effective in therapeutic cancer. GLUT3 is also highly expressed in GBM cells. Thus, we studied the tumorigenesis and apoptosis of GBM cells (U87MG and A172) by miR-622-regulated GLUT3 repression. miR-622 is highly correlated with apoptosis in GBM cells (U87MG and A172). MiR-622 significantly downregulated GLUT3 expression and induced apoptosis in GBM cells. Also, we showed that miR-622 suppressed the colony formation in GBM cells by colony formation assay. Additionally, we demonstrated that miR-622 induced apoptosis in GBM cells by the MTT and FACS analysis, and DNA damage by the TUNEL assay. The GBM tumor size decreased in orthotopic mouse model that was injected with miR-622. GLUT3 is essential for tumor metabolism and GLUT3 upregulation is involved in tumor progression and resistance to therapy. GLUT3-CDS was found to interact with miR-622. HDAC2 knockdown in GBM cells induces GBM cell death through miR-622 upregulation and GLUT3 downregulation. Thus, this study demonstrated that miR-622 expression in HDAC2-silenced GBM cells suppressed GLUT3 expression and induce GBM cell death.Maste

TNF alpha Enhances Tamoxifen Sensitivity through Dissociation of ER alpha-p53-NCOR1 Complexes in ER alpha-Positive Breast Cancer

Tamoxifen is widely used as a medication for estrogen receptor alpha (ER alpha)-positive breast cancer, despite the similar to 50% incidence of tamoxifen resistance. To overcome such resistance, combining tamoxifen with other agents is considered an effective approach. Here, through in vitro studies with ER-positive MCF7 cells and ER-negative MDA-MB-231 cells, validated by the use of xenograft mice, we investigated the potential of tumor necrosis factor alpha (TNF alpha) to enhance tamoxifen sensitivity and identified NCOR1 as a key downstream regulator. TNF alpha specifically degraded nuclear receptor corepressor 1 (NCOR1) in MCF7 cells. Moreover, knockdown of NCOR1, similar to TNF alpha treatment, suppressed cancer cell growth and promoted apoptosis only in MCF7 cells and MCF7 xenograft mice through the stabilization of p53, a tumor suppressor protein. Interestingly, NCOR1 knockdown with TNF alpha treatment increased the occupancy of p53 at the p21 promoter, while decreasing that of ER alpha. Notably, NCOR1 formed a complex with p53 and ER alpha, which was disrupted by TNF alpha. Finally, combinatorial treatment with tamoxifen, TNF alpha and short-hairpin (sh)-NCOR1 resulted in enhanced suppression of tumor growth in MCF7 xenograft mice compared to single tamoxifen treatment. In conclusion, TNF alpha promoted tamoxifen sensitivity through the dissociation of the ER alpha-p53-NCOR1 complex, pointing at NCOR1 as a putative therapeutic target for overcoming tamoxifen resistance in ER alpha-positive breast cancer