甲基硝基亚硝基胍对哈萨克族人群正常食管上皮细胞p16 和 FHIT 基因甲基化及其表达的影响

doi:10.3969/j.issn.1004-616x.2014.05.007

Abstract

Abstract:

OBJECTIVE: To investigate the effects of MNNG on methylation and expressions of p16 and FHIT genes in normal esophageal epithelial cells in Kazakhs. METHODS：Kazakh people’s normal esophageal epithelial cells were culture in vitro in medium containing MNNG concentrations of 0.00，0.75，1.50，and 3.00 mg/mL for 24 h. Methylation of p16 and FHIT were analyzed by methylmion specific PCR(MSP)，the mRNA and protein level of p16 and FHIT were measured by real time PCR (RT-PCR) and Western blot. RESULTS：Compared with the control group， p16 and FHIT gene methylation status did not change in treated groups，but the expressions of p16 mRNA and protein level in treated groups were significantly higher than the control group(P<0.05 or P<0.01). The expressions of FHIT mRNA level in 0.75 μg/mL group was significantly decreased compared with the control group(P<0.01)，but in 3.00 μg/mL group FHIT mRNA and protein levels were significantly increased(P<0.05). CONCLUSION：At certain concentration， MNNG could increase the expressions of p16 and FHIT in normal esophageal epithelial cells in Kazakhs.

Key words: Kazakhs, esophageal epithelial cells, p16, FHIT

YIN Dong，HUANG Si-yu，CHEN Yan. Effects of MNNG on methylation and expression of p16 and FHIT genes in normal esophageal epithelial cells in Kazakhs[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2014.05.007.

References

[1] 马俪珍，张健斌，孟培培. 食品中亚硝胺类化合物的危害及控制研究进展[J]. 食品与保鲜，2012，10(2)：1-4.

[2] Domenico P，Calogero S，Claudio C，et al. O6-alkylguanines， dietary N-nitroso compounds，and their precursors in gastric cancer[J]. Nutr Cancer，2001，39(1)：42-49.

[3] Blasiak J，Trzeciak A，Gasiorowska A，et al. Vitamin C and quercetin modulate DNA damaging effect of N-methyl-n'-nitro-n-nitrosoguanidine (MNNG)[J]. Plant Food Hum Nutr，2002， 57(1)：53-61.

[4] Yamashita S，Wakazono K，Sugimura T，et al. Profiling and selection of genes differentially expressed in the pylorus of rat strains with different proliferative responses and stomach cancer susceptibility[J]. Carcinogenesis，2002，23(6)：923-928.

[5] Takahashi H，Shikata N，Tsubura A. Immunohistochemical reaction patterns of keratins in MNNG induced shrew oesophageal carcinomas[J]. Virchows Archiv，1994，424(3)： 267-271.

[6] 赵燕，陈艳. 哈萨克、汉族食管癌p16基因甲基化及其表达的研究[J]. 新疆医科大学学报，2011，34(7)：29-32.

[7] 李磊，邓彦超，赵燕，等. 新疆哈萨克族和汉族食管癌患者FHIT基因甲基化及其与预后的关系[J]. 癌变·畸变·突变，2012，24(2)：54-57.

[8] 黄思语，阿尔孜古丽·吐尔逊，邓彦超，等. 哈萨克族食管正常上皮细胞的原代培养方法[J]. 新疆医科大学学报，2014，37(3)：277-279.

[9] Wang LD，Zhou Q，Yang CS. Esophageal and gastric cardia epithelial cell proliferation in northern Chinese subjects living in a high incidence area[J]. J Cell Biochem，1997，28(29)：159-165．

[10] 赵凤娟，云妙英，张严，等. 新疆哈萨克族食管癌研究进展[J]. 中央民族大学学报：自然科学版，2009，18(3)： 85-89.

[11] David B，Silvestre V，Mario FF. Molecular analysis of a multistep lung cancer model induced by chronic inflammation reveals epigenetic regulation of p16 and activation of the DNA damage response pathway[J]. Neoplasia，2007，9(10)：840-845.

[12] 张喆，郑荣生. 乳腺癌患者血清中p16基因甲基化状态的研究[J]. 临床肿瘤学杂志，2010，15(5)：21-24.

[13] 王凡，谢新纪，朴颖实，等. 食管鳞癌和反流性食管炎中p16和hMLH1基因甲基化的探讨[J]. 中华病理学杂志，2011，40(4)：537-539.

[14] Kyung KD，Seon KL，Yun ST，et al. Role of 5'-CpG island hypermethylation of the FHIT gene in cervical carcinoma[J]. J Gynecol Oncol，2009，19(2)：117-122.

[15] 方健，高燕宁. FHIT基因研究进展[J]. 中华病理学杂志，2003，26(4)：76-78.

[16] Mohammad R，Dhillon SV，Ahmad A，et al. Promoter hypermethylation in tumor suppressing genes p16 and FHIT and their relationship with estrogen receptor and progesterone receptor status in breast cancer patients from Northern India[J]. Translat Oncol，2009，2(4)：264-70.

[17] 郭晓青，刘艳凤，郭瑞霞，等. 食管癌变过程中p16和FHIT 甲基化与蛋白缺失表达关系的研究[J]. 现代预防医学，2008，13(14)：149-151，153.

[18] Mathew R，Arora S，Khanna R，et al. Alterations in Cyclin D1 expression in esophageal squamous cell carcinoma in the Indian population[J]. J Cancer Res Clin Oncol，2001，127(4)： 251-257.

[19] 谷化平，黄勇，尚培中. 细胞周期素D1和p16蛋白表达与胆管癌转移和预后的关系[J]. 肝胆胰外科杂志，2013， 26(3)：47-49，59.

[20] Hiroyuki M，Naoshi F，Nobuho T，et al. Aberrant P16(ink4a) methylation is a frequent event in colorectal cancers： prognostic value and relation to mRNA expression and immunoreactivity[J]. J Cancer Res Clin Oncol，2010，136(2)：323-331.

[21] 张德庆，陈东育，宋兆峰. FHIT蛋白及mRNA在食管癌组织中的表达及意义[J]. 中国实验诊断学，2011，18(1)：87-89.

[22] Yin DT，Wang L，Sun J，et al. Association of the promoter methylation and protein expression of fragile histidine triad (FHIT) gene with the progression of differentiated thyroid carcinoma[J]. Internat J Clin Experiment Pathol，2010，3(5)： 482-491.

Effects of MNNG on methylation and expression of p16 and FHIT genes in normal esophageal epithelial cells in Kazakhs

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	YIN Lu, MA Chengbin, LIU Ping, ZHANG Yi, ZHAO Xuejun. Value of P16/Ki-67 double staining combined with DNA ploidy analysis in ASCUS shunt [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 264-268.
[2]	XIAO Hongmei, WU Yi, ZHANG Ting, WANG Shaokang, SUN Guiju. Effects of microcystin-LR on apoptosis, and Caspase-3 and Caspase-9 expression in human normal esophageal epithelial cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(6): 418-421,426.
[3]	XU Yi, LI Xufeng, ZHANG Huixia, CHEN Yan. High expression of DNMT1 in MNNG-induced malignant transformation of Kazakh esophageal epithelial cell [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(6): 460-466.
[4]	LI Xufeng, ZHANG Huixia, KADIRYA·Abduwali, CHEN Yan. Effect of folic acid on MNNGtreated esophageal epithelial cells and expression of DNMT1 enzyme activity [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(6): 458-463.
[5]	LI Lei，DENG Yan-chao，ZHAO Yan，CHEN Yan. Methylation of the FHIT gene in esophageal carcinoma in Kazakh and Han and relationship with prognosis [J]. , 2012, 24(2): 132-135.
[6]	KANG Chun-yan1;XIAO Hong1;WU Yi-ming2;. Relationship between Methylation of FHIT and p16 Genes and Lung Cancer [J]. , 2009, 21(4): 291-294.
[7]	ZHOU Li， HUANG Ping， ZHU An-na. Relationships between Methylation of p16 Gene，Her-2 Expression and Serum CA125 Level with Clinicopathological Characteristics in Endometrial Carcinoma [J]. , 2009, 21(2): 141-144.
[8]	YANG Xia1,YANG Sheng_li1,, LU Quan_jun2， YAN Ai_hua1. Analysis on the Methylation of the Promoter of MGMT Gene and p16 Gene in Esophageal [J]. , 2008, 20(4): 254-257.
[9]	ZHANG Yin-juan, LU Gang, ZHANG Li-jie, SHAN Bao-en. The Relationship between Suppressive Effects of Cortex Periplocae on BT_549 Cells and Expression of p16 and p27 [J]. , 2008, 20(3): 216-219.
[10]	WANG Ping1， ZHANG Qing2, WANG Zu-yi2, CHENG Ze-nong1,YU Dong-hong1, WU Shi-wu1. Expression of FHIT and p16 in Non-small Cell Lung Cancers [J]. , 2007, 19(3): 242-246.
[11]	LI Tie-chen1，LIU Ping2，SUN Hui-lan1，XU Yu-qi1. Analysis of p16 Gene Deletion and Mutation in Breast Cancer [J]. , 2007, 19(1): 73-075.
[12]	SHAN Yu-juan, WANG Shu-ran, ZHAO Xiu-juan,WU Kun. Effects and Mechanisms of Sulforaphane on the Cell Cycle of Human Bladder Cancer Cell Lines [J]. , 2006, 18(6): 443-446.
[13]	DONG Lei,LU Shan-shan,YANG Kai-yan. Diagnostic Significance of P16 Protein Expression in Cervical Intraepithelial Neoplasia [J]. , 2006, 18(5): 395-397.
[14]	CHEN Xiao-yun1,3， KONG Wei-jia1， TAN Ying-xia2，LI He 3，FANG Wei-qing3. The Significance of Abnormal Fhit Gene Expression in Primary Laryngocarcinoma [J]. , 2006, 18(4): 284-289.
[15]	LIU xiu-fang;HE li-ping;Hu shang-ping;Guo feng-ying. Expression of P53 and P16 protein of Lung Tissues in Rats Exposed to Cooking Siritch Oil Fume [J]. , 2006, 18(1): 38-041.