Digestive Diseases and Sciences

, Volume 58, Issue 7, pp 2028–2037 | Cite as

Low Expression of CyclinH and Cyclin-Dependent Kinase 7 Can Decrease the Proliferation of Human Esophageal Squamous Cell Carcinoma

  • Jianguo Zhang
  • Xiaojing Yang
  • Yuchan Wang
  • Hui Shi
  • Chengqi Guan
  • Li Yao
  • Xianting Huang
  • Zongmei Ding
  • Yuejiao Huang
  • Huijie Wang
  • Chun ChengEmail author
Original Article



Increased expression of cyclinH (CCNH) and cyclin-dependent kinase 7 (CDK7) has a relationship with poor prognosis in most human cancers.


Investigate the expression of CCNH and CDK7 in human esophageal squamous cell carcinoma (ESCC) and the effect of chemotherapy on their expression.


Western blotting and immunohistochemistry were used to measure the expression of CCNH and CDK7 proteins in ESCC and adjacent normal tissue in 98 patients. We use Cell Counting Kit-8 and cell flow to analyze the effects of cisplatin and interference of CCNH and CDK7 in cell cycle process.


Immunohistochemical analysis showed that CCNH and CDK7 expression were significantly associated with unfavorable clinicopathologic variables. CCNH and CDK7 protein levels were elevated in ESCC tissues in comparison with adjacent normal tissues. Survival analysis revealed that CCNH and CDK7 overexpression were significantly associated with overall survival (P < 0.001). Cisplatin or interference of CCNH or CDK7 led cells to grow slowly. Overexpression of CCNH and CDK7 in TE1 cells can lead to resistance to cisplatin.


We can conclude that CCNH and CDK7 may play an important role in the tumorigenesis and development of ESCC. CCNH and CDK7 expression affected the chemotherapy of tumor.


Esophageal squamous cell carcinoma CyclinH CDK7 Tumor immunology Proliferation 



This work was supported by the National Basic Research Program of China (973 Program, No. 2011CB910604, and No. 2012CB822104); the National Natural Science Foundation of China (No. 81172879, No. 81201858); Natural Scientific Foundation of Jiangsu Province Grant (No. BK2012231); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Conflict of interest



  1. 1.
    Yu C, Chen K, Zheng H, et al. Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis. Carcinogenesis. 2009;30:894–901.PubMedCrossRefGoogle Scholar
  2. 2.
    Mohebbi M, Mahmoodi M, Wolfe R, et al. Geographical spread of gastrointestinal tract cancer incidence in the Caspian Sea region of Iran: spatial analysis of cancer registry data. BMC Cancer. 2008;8:137.PubMedCrossRefGoogle Scholar
  3. 3.
    Eloubeidi MA, Desmond R, Arguedas MR, et al. Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status. Cancer. 2002;95:1434–1443.PubMedCrossRefGoogle Scholar
  4. 4.
    Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–2252.PubMedCrossRefGoogle Scholar
  5. 5.
    Glade MJ. Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition. 1999;15:523–526.PubMedCrossRefGoogle Scholar
  6. 6.
    Medvec BR. Esophageal cancer: treatment and nursing interventions. Semin Oncol Nurs. 1988;4:246–256.PubMedCrossRefGoogle Scholar
  7. 7.
    Yang CX, Matsuo K, Ito H, et al. Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene–gene interactions. Asian Pac J Cancer Prev. 2005;6:256–262.PubMedGoogle Scholar
  8. 8.
    Bahmanyar S, Zendehdel K, Nyren O, et al. Risk of oesophageal cancer by histology among patients hospitalised for gastroduodenal ulcers. Gut. 2007;56:464–468.PubMedCrossRefGoogle Scholar
  9. 9.
    Johnell O, Kanis JA. An estimate of the worldwide prevalence, mortality and disability associated with hip fracture. Osteoporos Int. 2004;15:897–902.PubMedCrossRefGoogle Scholar
  10. 10.
    Guerenstein PG, Yepez EA, Van Haren J, et al. Floral CO(2) emission may indicate food abundance to nectar-feeding moths. Naturwissenschaften. 2004;91:329–333.PubMedCrossRefGoogle Scholar
  11. 11.
    Takeno S, Noguchi T, Kikuchi R, et al. Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma. Cancer. 2002;94:2874–2881.PubMedCrossRefGoogle Scholar
  12. 12.
    Teng Y, Sun AN, Pan XC, et al. Synergistic function of Smad4 and PTEN in suppressing forestomach squamous cell carcinoma in the mouse. Cancer Res. 2006;66:6972–6981.PubMedCrossRefGoogle Scholar
  13. 13.
    Luo KJ, Hu Y, Wen J, et al. CyclinD1, p53, E-cadherin, and VEGF discordant expression in paired regional metastatic lymph nodes of esophageal squamous cell carcinoma: a tissue array analysis. J Surg Oncol. 2011;104:236–243.PubMedCrossRefGoogle Scholar
  14. 14.
    Liu QY, Wu ZL, Lv WJ, et al. Developmental expression of cyclin H and Cdk7 in zebrafish: the essential role of cyclin H during early embryo development. Cell Res. 2007;17:163–173.PubMedCrossRefGoogle Scholar
  15. 15.
    Liu Y, Wang Y, Cheng C, et al. A relationship between p27(kip1) and Skp2 after adult brain injury: implications for glial proliferation. J Neurotrauma. 2010;27:361–371.PubMedCrossRefGoogle Scholar
  16. 16.
    Patel SA, Simon MC. Functional analysis of the Cdk7.cyclin H.Mat1 complex in mouse embryonic stem cells and embryos. J Biol Chem. 2010;285:15587–15598.PubMedCrossRefGoogle Scholar
  17. 17.
    Bartkova J, Zemanova M, Bartek J. Expression of CDK7/CAK in normal and tumor cells of diverse histogenesis, cell-cycle position and differentiation. Int J Cancer. 1996;66:732–737.PubMedCrossRefGoogle Scholar
  18. 18.
    Fei M, Lu M, Wang Y, et al. Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization. Med Oncol. 2009;26:178–185.PubMedCrossRefGoogle Scholar
  19. 19.
    Mouriaux F, Casagrande F, Pillaire MJ, et al. Differential expression of G1 cyclins and cyclin-dependent kinase inhibitors in normal and transformed melanocytes. Invest Ophthalmol Vis Sci. 1998;39:876–884.PubMedGoogle Scholar
  20. 20.
    Ali S. Role of c-kit/SCF in cause and treatment of gastrointestinal stromal tumors (GIST). Gene. 2007;401:38–45.PubMedCrossRefGoogle Scholar
  21. 21.
    Bauer S, Duensing A, Demetri GD, et al. KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Oncogene. 2007;26:7560–7568.PubMedCrossRefGoogle Scholar
  22. 22.
    Tornillo L, Terracciano LM. An update on molecular genetics of gastrointestinal stromal tumours. J Clin Pathol. 2006;59:557–563.PubMedCrossRefGoogle Scholar
  23. 23.
    Lolli G, Johnson LN. CAK-cyclin-dependent activating kinase: a key kinase in cell cycle control and a target for drugs? Cell Cycle. 2005;4:572–577.PubMedCrossRefGoogle Scholar
  24. 24.
    Wang B, Yin BL, He B, et al. Overexpression of DNA damage-induced 45 alpha gene contributes to esophageal squamous cell cancer by promoter hypomethylation. J Exp Clin Cancer Res. 2012;31:11.Google Scholar
  25. 25.
    Gopisetty G, Ramachandran K, Singal R. DNA methylation and apoptosis. Mol Immunol. 2006;43:1729–1740.PubMedCrossRefGoogle Scholar
  26. 26.
    Fisher RP, Morgan DO. A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase. Cell. 1994;78:713–724.PubMedCrossRefGoogle Scholar
  27. 27.
    Lepage C, Rachet B, Jooste V, et al. Continuing rapid increase in esophageal adenocarcinoma in England and Wales. Am J Gastroenterol. 2008;103:2694–2699.PubMedCrossRefGoogle Scholar
  28. 28.
    Stein HJ, von Rahden BH, Siewert JR. Survival after oesophagectomy for cancer of the oesophagus. Langenbecks Arch Surg.. 2005;390:280–285.PubMedCrossRefGoogle Scholar
  29. 29.
    Murakami K, Akutsu Y, Miyazawa Y, et al. A case of small-cell esophageal cancer with chronic renal failure undergoing hemodialysis safely treated with cisplatin and etoposide. Esophagus. 2011;8:209–215.PubMedCrossRefGoogle Scholar
  30. 30.
    Yamada H, Ochi K, Nakada S, et al. Interferon modulates the messenger RNA of G1-controlling genes to suppress the G1-to-S transition in Daudi cells. Mol Cell Biochem. 1995;152:149–158.PubMedCrossRefGoogle Scholar
  31. 31.
    te Poele RH, Okorokov AL, Joel SP. RNA synthesis block by 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) triggers p53-dependent apoptosis in human colon carcinoma cells. Oncogene. 1999;18:5765–5772.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jianguo Zhang
    • 1
  • Xiaojing Yang
    • 1
  • Yuchan Wang
    • 1
  • Hui Shi
    • 1
  • Chengqi Guan
    • 1
  • Li Yao
    • 1
  • Xianting Huang
    • 1
  • Zongmei Ding
    • 1
  • Yuejiao Huang
    • 1
  • Huijie Wang
    • 2
  • Chun Cheng
    • 1
    Email author
  1. 1.Department of Immunology, Medical CollegeNantong UniversityNantongPeople’s Republic of China
  2. 2.Department of Medical Oncology, Fudan University Shanghai Cancer CenterFudan UniversityShanghaiPeople’s Republic of China

Personalised recommendations