• Title/Summary/Keyword: RETINOIC ACID

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Suppression of Human GD3 Synthase (hST8Sia I) Expression Induced by Retinoic Acid in Human Melanoma SK-MEL-2 Cells (흑색종세포주 SK-MEL-2에서 레티노이드에 의한 GD3합성효소(hST8Sia I)의 발현억제)

  • Kwon, Haw-Young;Kang, Nam-Young;Lee, Young-Choon
    • Journal of Life Science
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    • v.20 no.5
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    • pp.655-661
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    • 2010
  • To elucidate the mechanism underlying the suppressive regulation of hST8Sia I expression in retinoic acid (RA)-induced SK-MEL-2 cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5‘-flanking region of the hST8Sia I gene by the transient expression method showed that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kB, functions as the RA-repressive promoter in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analyses indicated that the NF-kB binding site at -731 to -722 is crucial for the RA-induced repression of hST8Sia I in SK-MEL-2 cells. In addition, the transcriptional activity of hST8Sia I suppressed by RA in SK-MEL-2 cells was strongly inhibited by extracellular signal-regulated protein kinase (ERK) inhibitor U0126 and protein kinase C (PKC) inhibitor GO6976, as determined by RT-PCR and luciferase assay of hST8Sia I promoter containing the -1146 to -646 regions. These results suggest that RA markedly modulates transcriptional regulation of hST8Sia I gene expression through the PKC/ERK signal pathway in SK-MEL-2 cells.

Transglutaminase-2 Is Involved in All-Trans Retinoic Acid-Induced Invasion and Matrix Metalloproteinases Expression of SH-SY5Y Neuroblastoma Cells via NF-κB Pathway

  • Lee, Hye-Ja;Park, Mi-Kyung;Bae, Hyun-Cheol;Yoon, Hee-Jung;Kim, Soo-Youl;Lee, Chang-Hoon
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.286-292
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    • 2012
  • All-trans retinoic acid (ATRA) is currently used in adjuvant differentiation-based treatment of residual or relapsed neuroblastoma (NB). It has been reported that short-term ATRA treatment induces migration and invasion of SH-SY5Y via transglutaminase-2 (Tgase-2). However, the detailed mechanism of Tgase-2's involvement in NB cell invasion remains unclear. Therefore we investigated the role of Tgase-2 in invasion of NB cells using SH-SY5Y cells. ATRA dose-dependently induced the invasion of SH-SY5Y cells. Cystamine (CTM), a well known tgase inhibitor suppressed the ATRA-induced invasion of SH-SY5Y cells in a dose-dependent manner. Matrix metalloproteinase -9 (MMP-9) and MMP-2, well known genes involved in invasion of cancer cells were induced in the ATRA-induced invasion of the SH-SH5Y cells. Treatment of CTM suppressed the MMP-9 and MMP-2 enzyme activities in the ATRA-induced invasion of the SH-SY5Y cells. To confirm the involvement of Tgase-2, gene silencing of Tgase-2 was performed in the ATRA-induced invasion of the SH-SH5Y cells. The siRNA of Tgase-2 suppressed the MMP-9 and MMP-2 activity of the SH-SY5Y cells. MMP-2 and MMP-9 are well known target genes of NF-${\kappa}B$. Therefore the relationship of Tgase-2 and NF-${\kappa}B$ in the ATRA-induced invasion of the SH-SY5Y cells was examined using siRNA and CTM. ATRA induced the activation of NF-${\kappa}B$ in the SH-SY5Y cells and CTM suppressed the activation of NF-${\kappa}B$. Gene silencing of Tgase-2 suppressed the MMP expression by ATRA. These results suggested that Tgase-2 might be a new target for controlling the ATRA-induced invasion of NBs.

Effects of Triterpence Acids and Ginsenosides in Differentiation of HL-60 Promyelocytic Leckemia Cells (HL-60 세포에 대한 Triterpent Acids와 Ginsenosides의 분화효과)

  • Kang, Chang-Mo;Lee, Ho-Young;Kim, Shin-Il;Kim, Kyu-Won
    • Journal of Life Science
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    • v.8 no.2
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    • pp.162-166
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    • 1998
  • The acute myelogeous leukemia cell line, HL-60 is good model to examine leukemia differentiation with nitro blue terazolium reduction assay. We investigated that effect of triterpene acids and ginseng saponin on differentiation of HL-60 cells. Differentiation of HL-60 cells was induced in proportion to ,olar concentration by dibutylyl cAMP, ginseng saponin, lithocholic acid, ginsenoside RH2, and ginsenoside RH3.

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MOLECULAR CONTROLS OF EPIDERMAL GROWTH AND DIFFERENTIATION: TRANSFORMING GROWTH FACTORE

  • Son, Youngsook;Fuchs, Elaine
    • Toxicological Research
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    • v.7 no.2
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    • pp.209-229
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    • 1991
  • In the epidermis of skin, a fine balance exists between proliferating progenitor cells and terminally differentiating cells. We examined the effects of TGF-betas and retinoic acid (RA) on controlling this balance in normal human epidermal keratinocytes cultured under conditions where most morphological and biochemical features of epidermis in vivo are retained. Our results revealed marked and pleiotropic effects of both TGF-beta and RA on kerationcytes. In contrast to retinoids, TGF-betas acted on mitotically active basal cells to retard cell proliferation.

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Inducing effect of helenalin on the differentiation of HL-60 leukemia cells

  • KIm, Seung-Hyun;Kim, Tae-Sung
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.166.3-167
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    • 2003
  • Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits $NF-{\kappa}B$ DNA binding activity by selectively alkylating the p65 subunit of $NF-{\kappa}B$. Transcription factors such as $NF-{\kappa}B$ provide powerful target of drugs to use in the treatment of cancer. Human promyelocytic leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin $D_3{\;}[1,25-(OH)_2D_3]$ or all-trans-retinoic acid (ATRA), respectively. (omitted)

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