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1.
Tumour Biol ; 36(12): 9865-71, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26164001

ABSTRACT

SUMOylation is a post-translational modification exerted various effects on the target proteins. SUMOylation is a highly dynamic and reversible process, which has been shown to play an important role in tumorigenesis. However, the roles of sentrin/SUMO-specific proteases (SENPs), which mediate the reverse process of SUMOylation, in tumorigenesis remains largely unexplored. Here, we uncover a critical role of SENP6 in promoting gastric cancer cells growth via regulating the deSUMOylation of a transcription factor forkhead box protein M1 (FoxM1). We demonstrated that the mRNA and protein levels were elevated in gastric cancer tissues. Overexpression of SENP6 promoted, while RNA interference depletion of endogenous SENP6 inhibited gastric cancer cells growth and the ability of colony formation. By using biochemical assays, we identified FoxM1 as a novel substrate of SENP6 in gastric cancer cells. Thus, our data suggest that SENP6, which is highly expressed in gastric cancer cells, regulates the transcriptional activity and stability of FoxM1 through deSUMOylation.


Subject(s)
Carcinogenesis/genetics , Cysteine Endopeptidases/genetics , Forkhead Transcription Factors/metabolism , Stomach Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cysteine Endopeptidases/biosynthesis , Forkhead Box Protein M1 , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Humans , Protein Processing, Post-Translational/genetics , RNA, Messenger/biosynthesis , Stomach Neoplasms/pathology , Sumoylation/genetics
2.
Zhonghua Yi Xue Za Zhi ; 88(22): 1540-2, 2008 Jun 10.
Article in Chinese | MEDLINE | ID: mdl-18956635

ABSTRACT

OBJECTIVE: To investigate the expression and significance of Glypican-3 in colorectal cancer. METHODS: Immunohistochemistry was used to detect the expression of Glypican-3 in 200 specimens of colorectal cancer and adjacent non-cancerous tissues resected during operation. RESULTS: Glypican-3 immunoreactivity was recognized in both the cytoplasm and cellular membrane. The Glypican-3 positive expression rate in the tumor samples was 66.0% (132/200), significantly higher than that in the adjacent nontumor tissues (24%, 48/200, P = 0.019). The Glypican-3 expression rate was significantly correlated with the carcinoma invasion (P = 0.023) and lymph node metastasis (P = 0.015), but not associated with gender, age, tumor size, and differentiation grade (all P > 0.05). CONCLUSION: Over-expression of Glypican-3 may play an important role in the genesis and development of colorectal cancer, and may be used as a new biological parameter in predicting invasion and metastasis of colorectal carcinoma.


Subject(s)
Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Glypicans/biosynthesis , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness
3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 22(3): 290-2, 2006 May.
Article in Chinese | MEDLINE | ID: mdl-16643781

ABSTRACT

AIM: To construct the RNA interference eukaryotic expression vector specific for human MAD2 gene and to observe its effect on the growth of gastric cancer cell line SGC7901. METHODS: The expression vectors of pSilencer3.1/MAD2-siRNA1 and pSilencer3.1/MAD2-siRNA2 were constructed by gene recombination and then were stably transfected into the gastric carcinoma cell line SGC7901 by liposome mediation. The expression of MAD2 on the levels of protein and mRNA was detected by Western blot and RT-PCR, and the monoclone with the highest inhibition efficiency was selected. The growth of the transfected cells was assessed by MTT. And the cells treated with 1.0 mg/L vincristine (VCR) for 24 h were analyzed by FCM for cell cycle. RESULTS: Sequence-specific siRNAs targeting MAD2 significantly down regulated the expression of MAD2 in SGC7901 cells. In MAD2-siRNA transfected cells, the rate of cell growth increased markedly and cell cycle couldn't be arrested in M phase induced by VCR, while the cells transfected with the mock vector could. CONCLUSION: Down regulation of MAD2 expression of SGC7901 bv sequence-specific siRNA could accelerate the cell growth and impair the mitosis arrest of SGC7901 induced by VCR.


Subject(s)
Calcium-Binding Proteins/antagonists & inhibitors , Cell Cycle Proteins/antagonists & inhibitors , RNA, Small Interfering/metabolism , Repressor Proteins/antagonists & inhibitors , Stomach Neoplasms/pathology , Animals , Calcium-Binding Proteins/genetics , Carcinoma/pathology , Cell Cycle Proteins/genetics , Eukaryotic Cells , Gene Silencing/drug effects , Genetic Vectors/genetics , Humans , Mad2 Proteins , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Repressor Proteins/genetics
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 11(1): 70-3, 2003 Feb.
Article in Chinese | MEDLINE | ID: mdl-12667294

ABSTRACT

UNLABELLED: The purpose of this study was to evaluate the effects of cellular immunity activation on P58(+) cells expressing killer cell inhibitory receptor (KIR) and their regulatory function on cellular immunity, and provid theoretical data for preventing graft-vers-host disease (GVHD) in stem cell transplantation therapy. The mononuclear cells from human peripheral blood were incubated with IL-2, Con A and Lipostin (LP) for 72 hours. The KIR expressing cells, P58.1(+) and P58.2(+) cells, were analyzed by flow cytometry. The results showed that the percentages of CD3(+), CD4(+), CD8(+), CD16(+)CD56(+), P58.1(+) and P58.2(+) cells were greatly increased after treated with IL-2, Con A and LP, separately or in combination, and the percentages of above cells in combined treatment groups were higher than those of single stimulated groups, especially the percentage of cells in the IL-2 + LP group was significantly higher than those in IL-2 and LP singly treated groups. IN CONCLUSION: IL-2, Con A and LP possess the ability to induce the expression of KIR and stimulate proliferation of P58.1(+) and P58.2(+) cells while to activate the celluar immunity response, the expression of P58 gene may be regulated by the activation of cellular immunity.


Subject(s)
Leukocytes, Mononuclear/immunology , Receptors, Immunologic/analysis , Adult , CD3 Complex/analysis , CD4 Antigens/analysis , CD56 Antigen/analysis , CD8 Antigens/analysis , Cell Count , Cell Division/drug effects , Concanavalin A/pharmacology , Flow Cytometry , Humans , Interleukin-2/pharmacology , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Receptors, IgG/analysis , Receptors, KIR , Receptors, KIR2DL3
5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 19(1): 56-8, 2003 Jan.
Article in Chinese | MEDLINE | ID: mdl-15132908

ABSTRACT

AIM: To explore modulation of CD158+ cells in human peripheral blood by Th1-and Th2-like cytokines and provide basic data for inducing immune tolerance and preventing graft-versus-host disease (GVHD) in stem cells transplantation. METHODS: Peripheral blood mononuclear from healthy adults were cultured with Th1-like cytokines IL-2, IFN-gamma and Th2-like cytokines IL-4, IL-6 for 72 hours, rates of CD3+, CD4+, CD8+ cells, CD16+ CD56+ cells and CD158a+/b+ cells were analyzed by FACS. RESULTS: (1) The effects of cytokines on CD3+, CD4+, CD8+ and CD16+ CD56+ cells: the rates of above cells were greatly increased after being treated with IL-2 or IFN-gamma(P< 0.05), but efficacy of IL-2 was higher than that of IFN-gamma(P< 0.05). The rates of above cells in IL-2+IFN-gamma treated cells were higher than that in IL-2 or IFN-gamma treated alone. The rates of above cells were greatly decreased after being treated with IL-4+IL-6(P< 0.05), but efficacy of combination of IL-2+IL-4 was higher than that of IL-4 alone, lower than that of IL-2 alone (P< 0.05). (2) The effects of cytokines on CD158a+/b+ cells: the rates of CD158a+/b+ cells in total mononuclear and in CD3+, CD4+, CD8+ and CD16+ CD56+ cells were significantly raised after being treated with IL-2 (P< 0.01), but had no significance changes after being treated with IFN-gamma. The rates of CD158a+/b+ cells were decreased after being treated with IL-4+IL-6, whereas increased after being treated with IL-2+IFN-gamma(P< 0.05), but efficacy of being treated with IL-2+IL-4 was lower than that with IL-2(P< 0.05). CONCLUSION: IL-2 plays an important role in the regulation of CD158a/b expression or proliferation of CD158a+/b+ cells. It may involve in controlling NK cells and T cells activity via expression of regulating these molecules or stimulating proliferating of CD158a+/b+ cells. IL-4 and IL-6 have a slight ability to decrease the rates of CD158a+/b+ cells and IL-4 can partially reverse the effect of IL-2 on CD158a+/b+ cells.


Subject(s)
Interferon-gamma/pharmacology , Interleukin-2/pharmacology , Interleukins/pharmacology , Leukocytes, Mononuclear/immunology , Receptors, Immunologic/metabolism , Adult , Cells, Cultured , Humans , Interleukin-4/pharmacology , Interleukin-6/pharmacology , Leukocytes, Mononuclear/cytology , Male , Receptors, KIR , Receptors, KIR2DL1
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