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ABSTRACT: LeY (Lewis Y) is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of LeY is frequently observed in epithelial-derived cancers and is correlated to pathological staging and prognosis. To study the role of LeY on cancer cells, a stably LeY-overexpressing cell line, RMG-I-H, was developed previously by transfection of the α1,2-fucosyltransferase gene, a key enzyme that catalyzes the synthesis of LeY, into ovarian carcinoma-derived RMG-I cells. Our studies have shown that LeY is involved in the changes in biological behavior of RMG-I-H cells. However, the mechanism is still largely unknown. In this study, we determined the structural relationship and co-localization between LeY and TβRI/TβRII, respectively, and the potential cellular signaling mechanism was also investigated. We found that both TβRI and TβRII contain the LeY structure, and the level of LeY in TβRI and TβRII in RMG-I-H cells was significantly increased. Overexpression of LeY up-regulates the phosphorylation of ERK, Akt and down-regulates the phosphorylation of Smad2/3. In addition, the phosphorylation intensity was attenuated significantly by LeY monoantibody. These findings suggest that LeY is involved in the changes in biological behavior through TGF‑β receptors via Smad, ERK/MAPK and PI3K/Akt signaling pathways. We suggest that LeY may be an important composition of growth factor receptors and could be an attractive candidate for cancer diagnosis and treatment.
International Journal of Oncology 12/2011; 40(4):1196-202. · 2.40 Impact Factor
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ABSTRACT: INTRODUCTION: Castleman's disease is a rare disorder characterized by proliferation of the lymphoid tissue usually presenting as an asymptomatic mediastinal mass in children. The location of the disease in the mesentery is rare. DISCUSSION: We report a case of a 12-year-old girl with an isolated mass of mesenteric root presenting with vague abdominal pain. The surgical resection of the mass revealed the hyaline-vascular type of Castleman's disease. The patient had an uneventful postoperative course.
Journal of Gastrointestinal Surgery 05/2011; 15(10):1896-8. · 2.83 Impact Factor
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ABSTRACT: The aim of the study was to determine the spatiotemporal expression of Wnt5a during hindgut and anorectum development in human embryos and to explore the possible role of Wnt5a during the morphogenesis of the human hindgut and anorectum.
The embryos (n = 107) were sectioned serially and sagittally, using Wnt5a immunohistochemical staining on the caudal midline from the 4th-9th weeks of gestation.
From the 4th-7th week of gestation, the Wnt5a-positive cells were mainly located on the epithelium of the apical urorectal septum, hindgut, and cloacal membrane. After the anorectum and the urogenital sinus (UGS) opened to the amniotic cavity during the 7th week, the Wnt5a-positive cells disappeared and remained negative up to the 9th week on the epithelium of the anal canal.
The expression of Wnt5a was constantly active during human hindgut and anorectum development and disappeared after the anus formed, suggesting that Wnt5a plays an important role in human hindgut and anorectal morphogenesis.
International Journal of Colorectal Disease 03/2011; 26(8):983-8. · 2.38 Impact Factor
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ABSTRACT: Lewis(y) antigen is an oligosaccharide containing two fucoses, and is expressed variously in 75% of ovarian tumors, where its high expression level predicts poor prognosis. The effect and the possible mechanism of Lewis(y) on the proliferation of human ovarian cancer cells are still largely unkown. We report here that transfecting alpha1,2-FT gene into RMG-I cells increased the expression of Lewis(y) and promoted cell proliferation. In alpha1,2-FT-transfected cells, the Lewis(y) content of EGFR was increased dramatically. Tyrosine phosphorylation of EGFR was elevated. Concomitantly, tyrosine phosphorylation of Akt, ERK1/2 was also upregulated. Moreover, the expression of HER2/neu mRNA and protein, the tyrosine phosphorylation of HER2/ neu were also elveated, while the expression of p27 was significantly reduced. However, the expression of EGFR and the relative content of Lewis(y) on HER2/neu were unchanged. The above-mentioned alterations were correlated with the Lewis(y) content of EGFR and alpha1,2-FT expression in cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of alpha1,2-FT were attenuated significantly by the inhibitor of EGFR tyrosine kinase and by the mono-antibody to Lewis(y). Meanwhile, the reduction in p27 and the difference in its expression among the two cell lines were also blocked by the Lewis(y) antibody. The PI3K signaling pathway was more important than the MAPK pathway in the regulation of p27 expression. These findings provide strong evidence that increased expression of Lewis(y) promotes cell proliferation through regulating the phosphorylation and expression of some molecules involved in the EGFR/PI3K-signaling pathway.
Oncology Reports 03/2010; 23(3):833-41. · 1.84 Impact Factor
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ABSTRACT: To investigate the influence of Lewis y antigen on the gene expression of partial drug resistance associated proteins in human ovarian cancer cell line RMG-I-H.
RT-PCR was used to determine the gene expressions of partial drug resistance associated proteins in RMG-I-H cell line transfected with alpha1, 2-fucosyltransferases gene and RMG-I cell line, as well as in RMG-I-H treated with or without anti-Lewis y monoclonal antibody at the concentration of 10 micro/g/ml. The immunocytochemical method was used to detect the expression of P-glycoprotein (P-gp) in RMG-I and RMG-I-H cell lines. RMG-I and RMG-I-H cells were transplanted into nude mice and the expression of P-gp in the tissues was measured by immunohistochemistry.
The mRNA expressions of protein kinase C-alpha (PKC-alpha), topoismerase I ( Topo I ), multidrug resistance-associated protein-1 (MRP-1), and MRP-2 were significantly higher in RMG-I-H cells than those in RMG-I cells (0.46 +/- 0.02 vs. 0.27 +/- 0.05, 0.82 +/- 0.08 vs. 0.52 +/- 0.04, 0.66 +/- 0.07 vs. 0.34 +/- 0.12, and 0.44 +/- 0.08 vs. 0.23 +/- 0.05; all P < 0.05). However, the mRNA expression of multi-drug resistance 1 (MDR-1) was significantly lower in RMG-I-H cells than that in RMG-I cells (0.26 +/- 0.05 vs. 0.45 +/- 0.08, P < 0.05). The P-gp level increased in RMG-I-H cells compared with that in RMG-I cells both in vivo and in vitro (P < 0.05). Expressions of MDR-1, MRP-1, MRP-2, PKC-alpha, and Topo I mRNA decreased by the time in RMG-I-H cells treated with anti-Lewis y monoclonal antibody (all P < 0.05), while mRNA expressions of those genes in the control group did not statistically change (P > 0.05). In addition, MDR-1, MRP-1, MRP-2, PKC-alpha, and Topo I mRNA expressions were significantly lower in RMG-I-H cells treated with anti-Lewis y monoclonal antibody than those in the control group at 6 hours (all P < 0.05) and the inhibition ratios were 48.55%, 77.50%, 70.18%, 45.86%, and 46.13%, respectively.
The Lewis y antigen of the human ovarian cancer cell surface is closely correlated with the regulation on the gene expression of partial drug resistance associated proteins.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 08/2009; 31(4):481-7.
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ABSTRACT: To explore the effect of alpha1,2-fucosyltransferase (alpha1,2-FT) gene on the biological behavior of ovarian carcinoma cells, the expression vector pcDNA3.1 -HFUT-H which containing human alpha1,2-FT gene coding region was constructed and transfected into ovarian carcinoma cell line RMG-I. alpha1,2-FT gene expression, Lewis y antigen expression, alpha1,2-FT activity, rates of cell growth and tumorogenesis in nude mice were compared before and after RMG-I being transfected. The transfection of alpha1,2-FT gene significantly increased the expression of alpha1,2-FT gene and Lewis y antigen in RMG-I cells. After the transfection, RMG-I cells showed remarkable improvement of alpha1,2-FT activity, cell proliferation, the ability of colony formation in soft agar and tumorogenesis in nude mice. The growth rates of alpha1,2-FT gene transfected RMG-I cells were obviously increased, presenting that the proportion of the cells in G2-M and S phases was obviously increased from 2.05% to 7.32% and from 23.95% to 33.27% respectively, and that of the cells in G1 phase was obviously decreased from 74.14% to 59.46%, as compared with the control group. These findings indicate that alpha1,2-FT and Lewis y antigen have the ability to enhance the proliferation and elevate the survival rates of RMG-I cells, which can promote the genesis and development of ovarian carcinoma.
Journal of Molecular Cell Biology 01/2009; 41(6):435-42.
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ABSTRACT: The malignant biological behaviors are enhanced in human ovarian cancer cell line RMG-1 after transfection of alpha1,2-fucosyl transferase (alpha1,2-FT) gene. This study was to investigate the influence of alpha1,2-FT gene transfection on cancer-related gene expression profile of RMG-1 cells.
Gene expressing vector pcDNA3.1-HFT-H and empty vector pcDNA3.1 were transfected into RMG-1 cells to produce RMG-1-H and RMG-1-C cells separately. Gene expression profiles of these two cell lines were detected by gene chip assay. The acquired data were inquired on the GoMiner online database.
After transfection, comparing with those in RMG-1-C cells, 88 differentially expressed genes were identified in RMG-1-H cells: 60 were up-regulated and 28 were down-regulated. These genes are involved in protein binding, nucleotide binding, cell proliferation, DNA-dependent regulation of transcription, signal transduction, protein amino acid phosphorylation, transcription, cell adhesion, and so on.
The transfection of alpha1,2-FT gene causes the changes of gene expression profile in ovarian cancer RMG-1 cells.
Ai zheng = Aizheng = Chinese journal of cancer 10/2008; 27(9):934-41.
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ABSTRACT: To study the inhibitory effect of anti-Lewis y monoclonal antibody on proliferation, adhesion and invasion of alpha1, 2-fucosyltransferase gene transfected human ovarian cancer cell line RMG-I-H with over-expression of Lewis y antigen in vitro.
The changes of proliferation, adhesion and invasion of RMG-I-H cells in vitro were detected by cell growth assay, cell adhesive assay and cell invasive assay, respectively, with goat anti-human IgG antibody treated group or non-antibody treated group as control.
The proliferation and adhesion of RMG-I-H cells were remarkably inhibited by preincubation of the tumor cells with anti-Lewis y antibody in vitro (P<0.05). The growth inhibitory rate from the second day to the seventh day was 5.62%, 19.75%, 34.96%, 46.51%, 49.78% and 33.33%, respectively. The adhesion inhibitory rate at different time points (15, 30, 60 min) was 47.59%, 58.64% and 13.85%, respectively. Invasive assay with a transwell cell culture chamber showed that there were no significant differences of invasion in vitro between each concentration of the Lewis y antibody treated group and non-antibody treated group (P>0.05).
Anti-Lewis y antibody significantly inhibits the proliferation and adhesion of RMG-I-H cells cultured in vitro, but it has no effect on invasion, which indicates that Lewis y is associated with some biological behaviors, such as proliferation and adhesion. The antibody against Lewis y may be an effective anti-metastasis agent for the treatment of patients with ovarian cancer.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 04/2008; 24(3):267-9.
