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Article Epigenetic silencing of E- and P-cadherin gene expression in human melanoma cell lines. 2004
Tsutsumida A, Hamada J, Tada M, Aoyama T, Furuuchi K, Kawai Y, Yamamoto Y, Sugihara T, Moriuchi T. · Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan. · Int J Oncol. · Pubmed #15492833 No free full text.
Abstract: The degree of E- and P-cadherin expressions inversely correlate with the progression stage of human melanoma. In the present study, we analyzed mechanisms of down-regulation of E- and P-cadherin gene expressions in 8 human melanoma cell lines. In 5 of the 8 melanoma cell lines, E-cadherin expression was lost or markedly decreased compared to that in normal melanocytes, and 4 of the 5 melanoma cell lines lost P-cadherin expression. All of the melanoma cell lines expressed snail, which is known to encode a transcription repressor for E-cadherin, at a higher level than melanocytes whereas expression levels of the snail varied among cell lines. Transduction of snail gene into MMAc cells which expressed a high level of E-cadherin and an extremely low level of snail decreased expression of E-cadherin but not P-cadherin. In contrast, transduction of antisense-snail gene into A375M cells which expressed no E-cadherin and a high level of snail restored expression of E-cadherin but not P-cadherin. Methylation-specific PCR analysis revealed CpG methylation in the promoter region of E-cadherin of MeWo and AKI cells. Further, the treatment with a demethylating agent, 5-azacytidine led AKI and A375M cells to re-express both E- and P-cadherin. The results show E-cadherin gene is silenced by at least two distinct mechanisms (methylation and transrepression by Snail) in human melanoma cell lines whereas P-cadherin gene seems to be silenced by methylation but not by snail.
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Retraction [Effects of vascular endothelial growth factor D on the signaling cascade of sentinel lymphatic endothelial cells from melanoma patients undergoing sentinel lymphadenectomy] 2003
Kawai Y, Takeda A, Gershenwald JE. · Dept. of Surgical Oncology, University of Texas MD Anderson Cancer Center, USA. · Gan To Kagaku Ryoho. · Pubmed #14712780 No free full text.
Abstract: Advances in surgical treatment, including sentinel lymphadenectomy, permit the pathologic staging of regional lymph nodes most likely to contain metastasis by identifying afferent lymphatic channels, which specifically drain the primary tumor site. Recently, a new member of the angiogenic molecule in VEGF family, VEGF-D, has been identified that induces lymphangiogenesis via high-affinity binding to VEGFR-3. VEGF-D is predominantly expressed in lymphatic endothelium. We have previously developed a novel method for the isolation of anatomically-defined lymphatic endothelial cells (LECs) from human sentinel lymphatic channel during SLN biopsy. The effect of VEGF-D on the extracellular signal-regulated kinases (Erk)-1/2 and Akt signaling pathway was examined by Western blot analysis. VEGF-D (500 ng/ml) apparently upregulated phospho-p44/phospho-p42 activity in human isolated LECs by Western blot analysis, while phospho-Akt activity was not at all changed by VEGF-D exposure without the change of total p44/p42 and Akt expression. U0126 (20 microM), the MEK1/2 inhibitor, could completely block the VEGF-D induced phospholylation of Erk1/2 signaling pathway. These data demonstrate that VEGF-D induces p44/p42 in human LECs and suggests that this signaling pathway activation may be important in LEC biology and lymphoangiogenesis, which may lead to the progression of new strategies of cancer treatment.
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