Expression and clinical significance of CAK complex in estrogen receptorpositive breast cancer

Abstract

Abstract:Objective To evaluate the expression and clinical significance of cyclin dependent kinase (CDK)activating kinase (CAK) complex including CDK7, cyclin H and accessory protein menage a trios 1 (MAT1) in estrogen receptorpositive breast cancer. MethodsA total of 40 patients with estrogen receptorpositive breast cancer from Department of Galactophore, Baoji Maternal and Child Care Service Centre of Shaanxi Province were investigated in this study. Breast cancer tissues and adjacent normal tissues were obtained from patients undergoing surgery. The mRNA expressions of CDK7, cyclin H and MAT1 in two types of tissues were measured by realtime fluorescent quantitative (qRT)PCR, and their correlations with clinicopathologic features of patients were analyzed. ResultsThe expressions of CDK7, cyclin H and MAT1 in cancer tissues were 2.54±0.78, 2.21±0.56 and 2.46±0.58, while those in adjacent normal tissues were 1.26±0.30, 1.16±0.42 and 1.17±0.39, and there were significantly differences between different types of tissues (t=9.654, P<0.001; t=9.433, P<0.001; t=11.741, P<0.001). The higher expressions of cyclin H and MAT1 in patients′ cancer tissues had the lower clinical stage, with significant correlations (U=3.17, P=0.01; U=2.53, P=0.01). In addition, the tumors were smaller in patients with higher expression levels of MAT1 (χ2=14.16, P=0.01). ConclusionThe expressions of CAK complex CDK7, cyclin H and MAT1 are elevated in estrogen receptorpositive breast cancer patients. Cyclin H and MAT1 are closely associated with clinical grade, and MAT1 is also significantly associated with tumor size.

Key words:Breast neoplasms,Diagnosis,CAK complex

Li Dan, Hu Haifeng, Xia Xiulin. Expression and clinical significance of CAK complex in estrogen receptorpositive breast cancer[J]. Journal of International Oncology, 2017, 44(7): 500-503.

References

［1］ Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm［J］. Nat Rev Cancer, 2009, 9(3): 153-166. DOI: 10.1038/nrc2602. ［2］ Banyai G, Badi F, Coudreuse D, et al. Cdk1 activity acts as a quantitative platform for coordinating cell cycle progression with periodic transcription［J］. Nat Commun, 2016, 7: 11161. DOI: 10.1038/ncomms11161. ［3］ Su J, Zhou H, Tao Y, et al. HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia［J］. Cell Signal, 2015, 27(1): 47-60. DOI: 10.1016/j.cellsig.2014.10.003. ［4］ Risal S, Adhikari D, Liu K. Animal models for studying the in vivo functions of cell cycle CDKs［J］. Methods Mol Biol, 2016, 1336: 155-166. DOI: 10.1007/978-1-4939-2926-9_13. ［5］ Wang Q, Li M, Zhang X, et al. Upregulation of CDK7 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis［J］. Exp Mol Pathol, 2016, 100(3): 514-521. DOI: 10.1016/j.yexmp.2016.05.001. ［6］ Schwartz BE, Larochelle S, Suter B, et al. Cdk7 is required for full activation of Drosophila heat shock genes and RNA polymerase Ⅱ phosphorylation in vivo［J］. Mol Cell Biol, 2003, 23(19): 6876-6886. ［7］冀全博, 徐小洁, 张强, 等. 人细胞周期蛋白H基因的真核表达载体构建和表达及功能检测［J］. 细胞与分子免疫学杂志, 2014, 30(9): 941-943. DOI: 10.13423/j.cnki.cjcmi.007091. ［8］ Pitts TM, Davis SL, Eckhardt SG, et al. Targeting nuclear kinases in cancer: development of cell cycle kinase inhibitors［J］. Pharmacol Ther, 2014, 142(2): 258-269. DOI: 10.1016/j.pharmthera.2013.12.010. ［9］ Ali S, Heathcote DA, Kroll SH, et al. The development of a selective cyclindependent kinase inhibitor that shows antitumor activity［J］. Cancer Res, 2009, 69(15): 6208-6215. DOI: 10.1158/00085472.CAN090301. ［10］ Kwiatkowski N, Zhang T, Rahl PB, et al. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor［J］. Nature, 2014, 511(7511): 616-620. DOI: 10.1038/nature13393. ［11］陈万青, 郑荣寿. 中国女性乳腺癌发病死亡和生存状况［J］. 中国肿瘤临床, 2015, 42(13): 668674. DOI: 10.3969/j.issn.10008179.20150571. ［12］龚巍巍, 罗胜兰, 胡如英, 等. 2005—2010年浙江省女性乳腺癌、宫颈癌与卵巢癌生存率分析［J］. 中华预防医学杂志, 2014, 48(5): 366-369. DOI: 10.3760/cma.j.issn.02539624.2014.05.007. ［13］ LaubySecretan B, Scoccianti C, Loomis D, et al. 国际癌症研究机构工作组乳腺癌筛查简报［J］. 中国全科医学, 2015, 18(27): 3265-3267. ［14］谢杨, 周雪妍, 郝海平, 等. 核受体FXR代谢调控作用及肿瘤细胞增殖机制研究进展［J］. 生理学报, 2014, 66(2): 252-258. DOI: 10.13294/j.aps.2014.0030. ［15］ Ganuza M, Santamaría D. Cdk7: open questions beyond the prevailing model［J］. Cell Cycle, 2012, 11(19): 3519-3520. DOI: 10.4161/cc.21888. ［16］ Liang YC, Tsai SH, Chen L, et al. Resveratrolinduced G2 arrest through the inhibition of CDK7 and p34CDC2 kinases in colon carcinoma HT29 cells［J］. Biochem Pharmacol, 2003, 65(7): 1053-1060. ［17］ Zhang S, Liu JP, Xu FQ, et al. Gene silencing of MAT1 mediated by siRNA inhibits cell proliferation and invasion in pancreatic cancer in vitro［J］. ChinGer J Clin Oncol, 2008, 7(5): 280-282. DOI: 10.1007/s10330-008-0020-4.

[1]	Liu Na, Kou Jieli, Yang Feng, Liu Taotao, Li Danping, Han Junrui, Yang Lizhou.Clinical value of serum miR-106b-5p and miR-760 combined with low-dose spiral CT in the diagnosis of early lung cancer[J]. Journal of International Oncology, 2024, 51(6): 321-325.
[2]	Yuan Jian, Huang Yanhua.Diagnostic value of Hp-IgG antibody combined with serum DKK1 and sB7-H3 in early gastric cancer[J]. Journal of International Oncology, 2024, 51(6): 338-343.
[3]	Wang Ying, Liu Nan, Guo Bing.Advances of antibody-drug conjugate in the therapy of metastatic breast cancer[J]. Journal of International Oncology, 2024, 51(6): 364-369.
[4]	Zhang Ningning, Yang Zhe, Tan Limei, Li Zhenning, Wang Di, Wei Yongzhi.Diagnostic value of cervical cell DNA ploidy analysis combined with B7-H4 and PKCδ for cervical cancer[J]. Journal of International Oncology, 2024, 51(5): 286-291.
[5]	Chen Qi, Xu Chenyang, Wang Yin, Lei Dapeng.Current application status of hyperspectral imaging in the diagnosis and treatment of head and neck tumor[J]. Journal of International Oncology, 2024, 51(5): 298-302.
[6]	Sa Qiang, Xu Hangcheng, Wang Jiayu.Advances in immunotherapy for breast cancer[J]. Journal of International Oncology, 2024, 51(4): 227-234.
[7]	Yang Zhi, Lu Yiqiao, Gu Huayan, Ding Jialing, Guo Guilong.Research progress of tumor microenvironment mediated drug resistance in targeted therapy of breast cancer[J]. Journal of International Oncology, 2024, 51(4): 235-238.
[8]	Zhang Lili, Tan Ru, Fang Xueli, Yang Yu, Sang Zheng, Li Baosheng.Imaging diagnosis， pathological upgrade， and imaging technology progress of ductal carcinomain situof the breast[J]. Journal of International Oncology, 2024, 51(3): 166-169.
[9]	Peng Qin, Cai Yuting, Wang Wei.Advances on KPNA2 in liver cancer[J]. Journal of International Oncology, 2024, 51(3): 181-185.
[10]	Chen Boguang, Wang Sugui, Zhang Yongjie.Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer[J]. Journal of International Oncology, 2024, 51(2): 73-82.
[11]	Jin Xudong, Chen Zhongjian, Mao Weimin.Research progress on the role of MTAP in malignant mesothelioma[J]. Journal of International Oncology, 2024, 51(2): 99-104.
[12]	Gu Huayan, Zhu Teng, Guo Guilong.Breast microbiota and breast cancer： present and future[J]. Journal of International Oncology, 2024, 51(1): 55-58.
[13]	Huang Zhen, Chen Yongshun.Research progress of circulating tumor DNA in the diagnosis and treatment of hepatocellular carcinoma[J]. Journal of International Oncology, 2024, 51(1): 59-64.
[14]	Wang Jing, Xu Wenting.Value of NLR， CEA combined with coagulation indicators in the differential diagnosis of benign and malignant breast nodules with a diameter ≤ 1.0 cm[J]. Journal of International Oncology, 2023, 50(9): 520-526.
[15]	Feng Chengtian, Huang Furong, Cao Shiyu, Wang Jianyu, Nanding Abiyasi, Jiang Yongdong, Zhu Juanying.Relationships between HER2 protein expression and imaging features in HER2 positive breast cancer patients[J]. Journal of International Oncology, 2023, 50(9): 527-531.