[1]李雪梅,罗淑娟,车亚玲,等.Rap1酶激动剂C3G对Ⅰ型卵巢癌细胞增殖和侵袭的影响[J].第三军医大学学报,2015,37(17):1715-1719.
 Li Xuemei,Luo Shujuan,Che Yaling,et al.Effect of Rap1 activator C3G on proliferation and invasion in type Ⅰ ovarian cancer cells[J].J Third Mil Med Univ,2015,37(17):1715-1719.
点击复制

Rap1酶激动剂C3G对Ⅰ型卵巢癌细胞增殖和侵袭的影响(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
37卷
期数:
2015年第17期
页码:
1715-1719
栏目:
论著
出版日期:
2015-09-15

文章信息/Info

Title:
Effect of Rap1 activator C3G on proliferation and invasion in type Ⅰ ovarian cancer cells
作者:
李雪梅罗淑娟车亚玲令狐华
重庆医科大学附属第一医院妇产科
Author(s):
Li Xuemei Luo Shujuan Che Yaling Linghu Hua

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

关键词:
Ⅰ型卵巢癌OVCAR3C3G增殖侵袭
Keywords:
type Ⅰ ovarian cancer OVCAR3 cells C3G proliferation invasion
分类号:
R394.3; R730.23; R737.31
文献标志码:
A
摘要:

目的      探讨Rap1酶激动剂鸟苷酸交换因子(Crk SH3-domain-binding guanine nucleotide-releasing factor,C3G)对Ⅰ型卵巢癌恶性增殖及侵袭能力的影响。      方法      Western blot分别检测Ⅰ型和Ⅱ型人卵巢癌组织中C3G蛋白的表达水平;利用Ⅰ型卵巢癌细胞株OVAR3,构建外源性过表达C3G蛋白的细胞株,通过MTT、平板克隆、流式细胞学实验检测细胞的增殖和凋亡情况;Transwell检测细胞迁移、侵袭能力;Western blot检测细胞MMP-2、MMP-9的表达。      结果      Ⅰ型卵巢癌组织中C3G表达(0.377 6±0.083 1)与良性卵巢肿瘤(0.351 1±0.071 3)及正常对照类似,明显低于Ⅱ型卵巢癌组织[(0.873 5±0.174 6),P<0.05]。低转移潜能卵巢癌细胞株OVAR3在外源表达C3G后表现出增殖减慢(P<0.05,P<0.01),凋亡增加(P<0.05),但迁移和侵袭能力增强(P<0.05),MMP-2、MMP-9表达增高(P<0.05)。      结论      C3G蛋白有抑制增殖和促进侵袭作用,其在Ⅰ型卵巢癌组织中的低表达与其低转移潜能和膨胀型生长模式相关。

Abstract:

Objective       To investigate the effect of guanine nucleotide exchange factor Crk SH3-domain-binding guanine nucleotide-releasing factor (C3G) on malignant proliferation and invasion of type Ⅰ ovarian cancer.       Methods       C3G expression in 6 samples of  type Ⅰ and 43 samples of  Ⅱ ovarian cancer tissues was detected by Western blotting. Exogenous C3G was transferred into type Ⅰ ovarian cancer cell line OVCAR3, and MTT assay, plate clone assay and flow cytometry were performed to analyze cell proliferation and apoptosis. Transwell chamber assay was adopted to evaluate cell invasion and migration. MMP-2 and MMP-9 expressions were examined by Western blotting.        Results       C3G expression in type Ⅰ ovarian cancer tissues (0.377 6±0.083 1) was similar to that in benign tumor tissues (0.351 1±0.071 3) and normal controls (0.336 2±0.073 9), but was lower than that in type Ⅱ ovarian cancer tissues (0.873 5±0.174 6, P<0.05). After C3G was over-expressed in the OVAR3 cells, cell proliferation was inhibited (P<0.05), and cell apoptosis was increased (P<0.05). Meanwhile the migration and invasion capacity was enhanced (P<0.05), and the expression of MMP-2 and MMP-9 was up-regulated (P<0.05).       Conclusion       C3G can inhibit proliferation and promote invasion in OVCAR3 cells, and its low expression in type Ⅰ ovarian cancer is associated with swelling growth and low metastatic potential.

参考文献/References:

[1]Christie M,  Oehler M K. Molecular pathology of epithelial ovarian cancer[J].J Br Menopause Soc, 2006, 12(2): 57-63.
[2]Koshiyama M, Matsumura N, Konishi I. Recent concepts of ovarian carcinogenesis:  type Ⅰ and type Ⅱ[J].Biomed Res Int,  2014,  2014: 934261.
[3]张旭, 李刚. 鸟苷酸交换因子C3G对心肌细胞生存力的影响及其可能机制[J]. 第二军医大学学报, 2012, 33(11): 1172-1177.
[4]Lengyel E. Ovarian cancer development and metastasis[J]. Am J Pathol,  2010,  177(3): 1053-1064.
[5]Chrzanowska-Wodnicka M. Regulation of angiogenesis by a small GTPase Rap1[J].Vascul Pharmacol,  2010,  53(1/2): 1-10.
[6]Radha V,  Mitra A,  Dayma K,  et al. Signalling to actin:  role of C3G,  a multitasking guanine-nucleotide-exchange factor [J]. Biosci Rep,  2011,  31(4): 231-244.
[7]Birukova A A,  Tian X,  Tian Y,  et al. Rap-afadin axis in control of Rho signaling and endothelial barrier recovery[J]. Mol Biol Cell,  2013,  24(17): 2678-2688.
[8]Maia V,  Ortiz-Rivero S,  Sanz M,  et al. C3G forms complexes with Bcr-Abl and p38α MAPK at the focal adhesions in chronic myeloid leukemia cells:  implication in the regulation of leukemic cell adhesion[J]. Cell Commun Signal, 2013, 11(1): 9.
[9]Kloog Y,  Mor A. Cytotoxic-T-lymphocyte antigen 4 receptor signaling for lymphocyte adhesion is mediated by C3G and Rap1[J]. Mol Cell Biol,  2014,  34(6): 978-988.
[10]高一萌,  张 瑜,  李文燕,  等. C3G/Rap1和Dock180/Rac1信号通路在卵巢癌浸润中的作用[J]. 第三军医大学学报,  2012,  34(11):  1031-1034.
[11]罗淑娟,  车亚玲,  彭慧娟,  等. C3G在卵巢癌组织中的表达及其在 SKOV3 细胞增殖中的作用[J]. 第三军医大学学报,  2013,  35(14):  1471-1479.
[12]Kurman R J, Shih IeM. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer——shifting the paradigm[J]. Hum Pathol, 2011, 42(7): 918-931.
[13]Hills CA,  Kelland LR,  Abel G,  et al. Biological properties of ten human ovarian carcinoma cell lines:  calibration in vitro against four platinum complexes[J]. Br J Cancer,  1989,  59(4): 527-534.
[14]Chen H,  Wu X,  Pan Z K,  et al. Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis[J]Cancer Res,  2010,  70(23): 9979-9990.
[15]Dayma K,  Ramadhas A,  Sasikumar K,  et al. Reciprocal negative regulation between the guanine nucleotide exchange factor C3G and β-catenin[J].Genes Cancer 2012, 3(9/10): 564-577.
[16]Lutgendorf S K,  Lamkin D M,  Jennings N B,  et al. Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma[J]. Clin Cancer Res,  2008,  14(21):  6839-6846.
[17]Kessenbrock K,  Plaks V,  Werb Z. Matrix metalloproteinases:  regulators of the tumor microenvironment[J]. Cell,  2010,  141(1):  52-67.
[18]Guvakova M A,  Lee W S,  Furstenau D K,  et al. The small GTPase Rap1 promotes cell movement rather than stabilizes adhesion in epithelial cells responding to insulin-like growth factor Ⅰ[J]. Biochem J,  2014,  463(2): 257-270.
[19]Liu E,  Thant A A,  Kikkawa F,  et al. The Ras-mitogen-activated protein kinase pathway is critical for the activation of matrix metalloproteinase secretion and the invasiveness in v-crk-transformed 3Y1[J].Cancer Res, 2000, 60(9): 2361-2364.
[20]Che Y L,  Luo S J,  Li G,  et al. The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis[J]. Cancer Lett,  2015,  359(2): 241-249.
[21]Brown P O,  Palmer C. The preclinical natural history of serous ovarian cancer:  defining the target for early detection[J]. PLoS Med,  2009,  6(7): e1000114.

更新日期/Last Update: 2015-09-07