低氧诱导因子-2α与CITED2、PTPRZ1在甲状腺乳头状癌中的表达及意义

孙琳 高彬 王冬梅 张文静 张静 吴靖芳

解剖学报 ›› 2016, Vol. 47 ›› Issue (6) : 785-790.

PDF(606 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(606 KB)
解剖学报 ›› 2016, Vol. 47 ›› Issue (6) : 785-790. DOI: 10.16098/j.issn.0529-1356.2016.06.011
肿瘤生物学

低氧诱导因子-2α与CITED2、PTPRZ1在甲状腺乳头状癌中的表达及意义

  • 孙琳1 高彬2 王冬梅3 张文静3 张静3 吴靖芳3*
作者信息 +

Expression and significance of hypoxia inducible factor 2α together with CITED2 and PTPRZ1 in thyroid papillary carcinoma

  • SUN Lin1 GAO Bin2 WANG Dong-mei3 ZHANG Wen-jing3 ZHANG Jing3 WU Jing-fang 3*
Author information +
文章历史 +

摘要

目的 通过检测低氧诱导因子-2α(HIF-2α)、CITED2和PTPRZ1在甲状腺乳头状癌(PTC)中的表达;分析三者在PTC发生、发展中的作用及临床意义,探讨HIF-2α在PTC中的作用机制。 方法 采用免疫组织化学法、Western blotting及Real-time PCR法检测HIF-2α、CITED2和PTPRZ1在50例甲状腺乳头状癌中的表达,并分析三者的变化与临床病理特征的关系。 结果 PTC组织中HIF-2α、CITED2和PTPRZ1的mRNA和蛋白表达水平明显高于三者在甲状腺腺瘤组织和瘤旁正常组织中的表达(P<0.05),且蛋白表达量与PTC淋巴结转移、病理分期及肿瘤大小有关(P<0.05),而与PTC患者年龄、性别无关(P>0.05)。 结论 在PTC中HIF-2α、CITED2和PTPRZ1蛋白的高表达与肿瘤的淋巴结转移、大小和临床病理分期呈正相关,HIF-2α可能通过CITED2和PTPRZ1的高表达促进PTC的发生、发展、侵袭及转移,三者在PTC的发生、发展和转移的过程中起重要的作用。

Abstract

Objective To analyze the role and clinical significance of hypoxia inducible factor 2α(HIF-2α),CITED2 and PTPRZ1 during the development of papillary thyroid carcinoma (PTC) by detecting the expressions of HIF-2α,CITED2 and PTPRZ1 in the PTC tissues. Methods The expressions of HIF-2α,CITED2 and PTPRZ1 proteins in 50 cases of PTC were detected by Western blotting and immunohistochemical SP method, and the relationships with the clinical pathology characteristics were analyzed.The transcriptional level changes of HIF-2αmRNA,CITED2mRNA and PTPRZ1mRNA were tested by real-time reverse transcription polymerase chain reaction. Results The positive expression rate of HIF-2α CITED2 and PTPRZ1 in PTC tissues were obviously higher than that in thyrvid adenoma(TA) group and normal thyroid(N) group(P<0.01)and expressions between N and TA were no significant difference (P>0.05). The expressions of HIF-2α, CITED2 and PTPRZ1 were unrelated to the age, sex and size of the tumor (P>0.05) of PTC patients, but associated with the lymph node metastasis and pathological stage (P<0.05). The transcriptional expression levels of the HIF-2α mRNA, CITED2 mRNA and PTPRZ1 mRNA in PTC tissues were significantly higher than in TA and normal tissues adjacent to the tumors with statistical significance(P<0.05), but there was no statistical difference between in TA and normal tissues adjacent to the tumors (P>0.05). Conclusion The higher expressions of HIF-2α, CITED2 and PTPRZ1 in PTC have a positive correlation with the lymph node metastasis, size and clinicopathologic stage. HIF-2α may promote the occurrence, development, invasion and metastasis of PTC by the higher expression of CITED2 and PTPRZ1.All of them play an important role in the process of PTC, include the occurrence, development, invasion and metastasis.

关键词

低氧诱导因子-2α / CITED2 / PTPRZ1 / 甲状腺乳头状癌 / 免疫组织化学 / 免疫印迹法 /

Key words

Hypoxia inducible factor 2α / CITED2 / PTPRZ1 / Papillary thyroid carcinoma / Immunohistochemistry / Western blotting / Human

引用本文

导出引用
孙琳 高彬 王冬梅 张文静 张静 吴靖芳. 低氧诱导因子-2α与CITED2、PTPRZ1在甲状腺乳头状癌中的表达及意义[J]. 解剖学报. 2016, 47(6): 785-790 https://doi.org/10.16098/j.issn.0529-1356.2016.06.011
SUN Lin GAO Bin WANG Dong-mei ZHANG Wen-jing ZHANG Jing WU Jing-fang. Expression and significance of hypoxia inducible factor 2α together with CITED2 and PTPRZ1 in thyroid papillary carcinoma[J]. Acta Anatomica Sinica. 2016, 47(6): 785-790 https://doi.org/10.16098/j.issn.0529-1356.2016.06.011

参考文献

[1]Siegel R, Naishadham D, Jemal A. Cancer statistics,2013 [J]. CA Cancer J Clin, 2013, 63(1): 11-30.
[2]Bergstrom JP, Helander A. Clinicalcharacteristics of carbohydrate deficient transferri n(disialotransferrin)measured by HPLC: sensitivity, specificity,gender effects,and relat-ionship with other alcohol biomarkers[J]. Alcohol, 2008,43(4):436-441.
[3]Brahimi-Horn MC, Chiche J, Pouyssegur J. Hypoxia and cancer[J].J Mol Med(Ber1),2007,85(12): 1301-1307.
[4]Wang V, Davis DA, Veeranna RP.et al. Characterization of the activation of protein tyrosine phospha tase, receptortype, Z polypeptide 1(PTPRZ1)byhypoxia inducible factor-2  alpha[J].PLoS One,2010,5(3):e9641.
[5]Weidemann A, Johnson RS. Biology of  HIF-1α[J]. Cell Death Differ, 2008, 15(4): 621-627.
[6]Tao BB, Zhang CC, Liu ShY, et al. Involvement of HIF-1 in the migration-promoting effects of hydrogen sulfide in vascular endothelial cells under normoxic conditions[J].Acta Physiologica Sinica, 2012, 64(2): 129-134.(in Chinese)
陶蓓蓓,张彩彩,刘姝媛,等.低氧诱导因子1参与常氧条件下硫化氢促血管内皮细胞迁移的作用[J].生理学报,2012, 64(2): 129-134. 
[7]Song B,Song XR, Wei L, et al.Effects of hypoxia on the expressions of HIF subunits HIF-1α, HIF-2α and HIF-β in human lung cancer cell lines and their correlations[J]. Acta Anatomica Sinica, 2008,39(6):850-853. (in Chinese)
宋宝,宋现让,巍玲,等.乏氧对肺癌细胞系HIF家族成员HIF-1α、HIF-2α和HIF-β表达的影响及其相关性[J].解剖学报,2008,39(6):850-853.
[8]Sandlund J, Ljungberg B, Wikstrom P, et al. Hypoxia-inducible factor-2 alpha mRNA expression in human renal cell carcinoma[J].Acta Oncol,2009,48(6): 909-914.
[9]Li N, Wang HX, Zhang J, et al. siRNA interference of hypoxia inducible factor 2α invasion ability of breast cancer cells and its mechanism[J]. Chinese Journal of Gerontology, 2015,35(8):2171-2173. (in Chinese)
李娜,王洪兴,张洁,等. siRNA干扰缺氧诱导因子2α对乳腺癌细胞侵袭能力的影响及相关机制[J]. 中国老年学杂志,2015,35(8):2171-2173.
[10]AekerT,Die-Juan A,Aragones J,et al. Genetic evidence for atumor suppressor role of HIF-2alPha [J].Caneer Cell,2005,8(2):131-141.
[11]Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF [J]. Science, 2001, 294(5545): 1337-1340.
[12]Aprelikova O, Wood M, Tackett S, et al. Role of ETS transcription facto rs in the hypoxia-inducible factor-2 target gene selection [J].Cancer Res, 2006,66 (11): 5641-5647.
[13]Liu YL, Song XR. Structure, expression and regulation of hypoxia-inducible factor[J]. Chinese Journal of Biochemistry and Molecular Biology, 2006,22(1):1-8. (in Chinese)
柳永蕾,宋现让. 乏氧诱导因子结构、表达及调控[J]. 中国生物化学与分子生物学报,2006,22(1):1-8.
[14]Shang S, Xu X, Wang D,et al. Protein tyrosine phosphatases enhances proliferation by increasing β-catenin nuclear expression in VHL-inactive human renal cell carcinoma cells[J]. World J Urol, 2013,3(6):1-8.
[15]Foehr E, Lorente G, Kuo J, et al. Targeting of the receptor protein tyrosine phosphatase beta with a monoclonal antibody delays tumor growth in a gliobl astoma model[J]. Cancer Res, 2006,66(4):2271-2278.

基金

河北省教育厅青年基金;河北省卫生厅医学研究课题;河北省教育厅重点项目;河北北方学院青年基金项目;河北北方学院面上基金项目


PDF(606 KB)

Accesses

Citation

Detail

段落导航
相关文章

/