Abstract：Objective: To investigate the role and mechanism of LGR5 in cervical carcinogenesis. Methods: The expression of LGR5 and β-catenin in normal cervix, cervical intraepithelial neoplasias and squamous cervical cancer were determined by immunohistochemistry and western blot, and analyze the relationship between LGR5 and clinical pathological features of cervical cancer and β-catenin expression. The effect of LGR5 on cervical carcinogenesis was examined using tumorsphere formation. Results: The positive rate of LGR5 and β-catenin in normal cervix, cervical intraepithelial neoplasias and cervical cancer were 17% (5/30), 65% (11/17), 84% (54/64) and 13%(4/30),53%(9/17),92%(59/64),respectively. The difference was statistically significant (P<0.01). The expression of LGR5 was associated with pathological grade of cervical cancer, but not with patient's age, clinical stage and lymph node metastasis. β-catenin expression in cervical cancer was positively related to LGR5 expression(r=0.69, P<0.01). Moreover, the rate of tumorsphere formation of LGR5 overexpression SiHa cell was significantly higher than the GFP control group (P<0.01). Conclusion: LGR5 and promoted cervical carcinogenesis and its mechanismmay be associated with high expressio0n of β--catenin
陈庆, 李向红, 赵金燕, 卢晓宁, 薛翔. LGR5在宫颈癌发生中的作用及机制初探[J]. 河北医学, 2017, 23(9): 1455-1458.
CHEN Qing, LI Xianghong, ZHAO Jinyan, et al. The Role and Mechanism of LGR5 in Cervical Carcinogenesis. 河北医学, 2017, 23(9): 1455-1458.
[1] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA: a cancer journal for clinicians, 2011, 61 (2): 69~90. [2] Barker N, Clevers H. Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells[J].Gastroenterology, 2010, 138 (5): 1681~1696. [3] He S, Zhou H, Zhu X, et al. Expression of Lgr5, a marker of intestinal stem cells, in colorectal cancer and its clinicopathological significance[J].Biomed Pharmacother, 2014, 68 (5): 507~513. [4] Zheng ZX, Sun Y, Bu ZD, et al. Intestinal stem cell marker LGR5 expression during gastric carcinogenesis[J].World Gastroenterol, 2013, 19 (46): 8714~8721. [5] Tanese K, Fukuma M, Yamada T, et al. G-protein-coupled receptor GPR49 is up-regulated in basal cell carcinoma and promotes cell proliferation and tumor formation[J].Am Pathol, 2008, 173: 835~843. [6] Fan X-S, Wu H-Y, Yu H-P, et al. Expression of Lgr5 in human colorectal carcinogenesis and its potential correlation with beta-catenin[J].Int Colorectal Dis, 2010, 25: 583~590. [7] Wang Y, Cai N, Wu X, et al. OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway[J].Cell Death Dis, 2013, 4 (8): e760. [8] Schepers AG, Snippert HJ, Stange DE, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas[J].Science, 2012, 337 (6095): 730~735. [9] Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008[J].International journal of cancer, 2010, 127 (12): 2893~2917. [10] Saavedra KP, Brebi PM, Roa JCS. Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix[J].Clinical Epigenetics, 2012, 4 (1): 1~7. [11] Yang L, Tang H, Kong Y, et al. LGR5 Promotes Breast Cancer Progression And Maintains Stem-like Cells Through Activation Of Wnt/β-Catenin Signaling[J].Stem Cells, 2015, 33 (10): 2913~2924. [12] Haegebarth A, Clevers H. Wnt signaling, lgr5, and stem cells in the intestine and skin[J].Am Pathol, 2009, 174 (3): 715~721. [13] Chai R, Xia A, Wang T, et al. Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea[J].Assoc Res Otolaryngol, 2011, 12 (4): 455~469. [14] Carmon KS, Lin Q, Gong X, et al. LGR5 interacts and cointernalizes with Wnt receptors to modulate Wnt/beta-catenin signaling[J].Mol Cell Biol, 2012, 32 (11): 2054~2064.
2017, Vol. 23 
冀公网安备13080202000677号