http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
MOON, Aree,KIM, Mi-Sung,KIM, Tae-Gyun,KIM, Seung-Hee,KIM, Harold E,CHEN, Yong Q,Choi Kim, Hyeong-Reh 德成女子大學校 藥學硏究所 1999 藥學論文誌 Vol.10 No.1
Elevated p21ras expression is associated with tumor aggressiveness in breast cancer including the extent of invasion into fat tissues, infiltration into lymphatic vessels and tumor of H-ras and N-ras, members of the human ras gene family, in the pathogenesis of breast cancer. We show that H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells (MCF10A) as determined by the Matrigel invasion assay, whereas both H-ras and N-ras induce anchorage-independent growth, as shown by soft agar assay. We examined the effects of H-ras and N-ras activation on the expression of MMP-2 and MMP-9, which can degrade type IV collagen, the major structural collagen of the basement membrane. We show that MMP-2 is efficiently induced by H-ras, whereas MMP-9 induction is more prominent in N-ras activated MCF10A cells. We also show that H-ras-mediated invasiveness is significantly inhibited when the expression of MMP-2 is down-regulated, using an oligodeoxyribonucleotide complementary to the MMP-2 mRNA, or when MMP-2 activity is blocked by its inhibitor TIMP-2(tissue inhibitors of matrix metalloproteinase-2). Our results show that the H-ras-induced invasive phenotype is associated more closely with the expression of MMP-2 in human breast epithelial cells, rather than the induction of MMP-9 expression, as shown previously for rat embryonic fibroblasts.
Kim, Mi-Sung,Lee, Eun-Jung,Choi Kim, Hyeong-Reh,Moon, Aree 德成女子大學校 藥學硏究所 2003 藥學論文誌 Vol.14 No.1
Ras expression has been suggested as a marker for tumor aggressiveness of breast cancer, including the degrees of invasion and tumor recurrence. We showed previously that H-ras, but not N-ras, up-regulates matrix metalloproteinase 2 expression and induces invasive phenotype in MCF10A human breast epithelial cells (A. Moon, et al. Int. J. Cancer, 85: 176-181, 2000). In this study, we show that H-ras also promotes cell motility more effectively than N-ras in MCF10A cells. We have investigated H-ras-specific signaling pathway(s) critical for H-ras-mediated cell motility and invasive phenotype. Whereas neither H-ras nor N-ras activated c-Jun NH_(2)-terminal kinase 1, both H-ras and N-ras effectively activated extracellular signal-regulated protein kinase (ERK)-1,2. Importantly, prominent activation of p38 mitogen-activated cells but not in N-ras activated MCF10A cells. Functional significance of H-ras activated p38 in invasiveness and cell motility was evidenced by studies using SB203580, a chemical inhibitor of p38, and a dominant-negative construct of p38. Whereas inhibition of c-Jun NH_(2)-terminal kinase 1 activity had noeffect on H-ras induced MCF10A cell invasion and motility, the inhibition of the ERK pathway using a chemical inhibitor PD98059 or dominant-negative mutant of mitogen-activated protein/ERK kinase 1, an activator of ERKs, significantly reduced H-ras-induced invasion and migration. We also provide evidence that p38 and, to a lesser degree, ERKs, are critical for H-ras-mediated up-regulation of matrix metalloproteinase 2. Taken together, the present study shows that H-ras activation of both p38 and ERKs induces cell invasion and motility, whereas N-ras activation of ERKs alone is not sufficient. This study reveals the p38 kinase as a key signaling molecule differentially regulated by H-ras and N-ras, leading to H-ras-specific cell invasive and migrative phenotypes in human breast epithelial cells.
Platelet-derived Growth Factor Signaling and Human Cancer
Yu, Jiuhong,Ustach, Carolyn,Choi Kim, Hyeong-Reh 한국생화학분자생물학회 2003 BMB Reports Vol.36 No.1
Platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. The vital functions of PDGFs for angiogenesis, as well as development of kidney, brain, cardiovascular system and pulmonary alveoli during embryogenesis, have been well demonstrated by gene knock-out approaches. Clinical studies reveal that aberrant expression of PDGF and its receptor is often associated with a variety of disorders including atherosclerosis, fibroproliferative diseases of lungs, kidneys and joints, and neoplasia. PDGF contributes to cancer development and progression by both autocrine and paracrine signaling mechanisms. In this review article, important features of the PDGF isoforms and their cell -surface receptor subunits are discussed, with regards to signal transduction, PDGF-isoform specific cellular responses, and involvement in angiogensis, and tumor-stromal interactions.
Yu, Jiuhong,Moon, Aree,Kim Choi, Reh Hyeong 德成女子大學校 藥學硏究所 2001 藥學論文誌 Vol.12 No.1
Cell motility plays a critical role for many physiological and pathological processes including wound healing, fibrosis, angiogenesis, and tumor metastasis. Platelet-derived growth factor (PDGF) is among the most potent stimuli for mesenchymal cell migration. The PDGF B-chain homodimer PDGF BB activates both α- and β-receptor subunits (α-PDGFR and β-PDGFR), and promotes cell migration in many cell types including fibroblasts and smooth muscle cells. PDGF-A chain homodimer PDGF AA activates α-PDGFR only, and its role for cell migration is still debatable. PDGF BB, but not PDGF AA, induces smooth muscle cell migration. Interestingly, α-PDGFR was shown to antagonize β-PDGFR-induced smooth muscle cell migration. In the present study, we investigated the role of α-PDGFR and β-PDGFR in PDGF-mediated cell migration of murine fibroblasts (NIH3T3). Unlike smooth muscle cells, both PDGF AA and PDGF BB promoted NIH 3T3 cell migration. The effect of PDGF BB activation of β-PDGFR alone for cell migration was examined using previously established NIH 3T3 clones in which α-PDGFR signaling is inhibited by a dominant-negative α-PDGFR, or an antisense construct of α-PDGFR. PDGF BB activation of β-PDGFR alone was sufficient to induce cell migration, but the efficiency was significantly lower compared to PDGF actlvation of both receptors. These results showed that both α- and β-PDG FRs promote fibroblast cell migration and their effects are additive. Taken together, we propose that cell-type specific α-PDGFR signaling is critical for regulation of mesenchymal cell migration in response to PDGF isoform, whereas β-PDGFR mainly promotes cell migration. ⓒ 2001 Academic Press
KANG, Hye-Jung,SOH, Yunjo,KIM, Mi-Sung,LEE, Eun-Jung,SURH, Young-Joon,KIM Choi, Hyeong-Reh,KIM, Seung Hee,Moon, Aree 德成女子大學校 藥學硏究所 2002 藥學論文誌 Vol.13 No.1
Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the majorpungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras-transformed cells of a common origin: parental (MCF10A) and H-ras transformed (H-ras MCF10A) human breast epithelial cells. Here, we show that capsalcin selectively induces apoptosis in H-ras-transformed cells but not in their normal cell counterparts. The capsaich-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H-ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK)while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H-ras-transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras-downstream signaling molecules in ras-activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis.