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Article

CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages

  • Authors:
    • Yang Yang
    • Biao Ma
    • Ling Li
    • Ye Jin
    • Wei Ben
    • Dandan Zhang
    • Keping Jiang
    • Shujun Feng
    • Lu Huang
    • Jianhua Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, School of Computing, University of Kent, Canterbury, Kent, CT2 7NF, UK
  • Pages: 2759-2768
    |
    Published online on: April 3, 2014
       https://doi.org/10.3892/or.2014.3127
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Abstract

A large quantity of M2-polarized tumor-associated macrophages (TAMs) is present in the tissue, ascitic fluid and peritoneum of ovarian cancer patients. A thorough understanding of the roles of M2-TAM in the development of ovarian cancer may provide new insight into the treatment of this disease. The rapid advancement of omics techniques presents a great challenge to biologists to extract meaningful biological information from vast pools of data. In the present study, using microarray method, we identified 996 genes in SKOV3 ovarian carcinoma cells that underwent expression level changes under the influence of TAMs. Subsequently, based on the protein-protein interactions network and the differentially expressed genes, a network showing the influence of TAMs on SKOV3 cells was constructed. The resulting network was analyzed with CFinder software and four modules were found; these modules were further analyzed using David software to perform functional annotations. It was found that module I was mainly related to tumorigenesis and cell cycle. Hence, 31 genes in module I were analyzed with Cytoscape software to generate a gene-function network, which revealed that four gene proteins (E2F1, RB1, CDK2 and CDK4) were functional. Based on literature review, we postulated that CDK2 and CDK4 were key players in the network. In the subsequent molecular experiments, western blot analysis and kinase activity detection demonstrated that TAMs can significantly boost the expression levels and activities of CDK2 and CDK4 in SKOV3 cells. With 3H-TdR incorporation and flow cytometry assay, the proliferation and cell cycle distribution of SKOV3 cells were detected in the absence or presence of CDK2 and CDK4 inhibitors and the results confirmed that the two kinases played a key role in TAM cells enhancing SKOV3 cell proliferation by promoting G0/G1 to S transition. In the present study, we identified the specific changes in the gene expression profile of SKOV3 cells under the influence of TAMs and explored a method for analyzing the gene expression profile data. The results may aid in the design of subsequent molecular experiments.
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View References

1 

Yin F, Liu X, Li D, Wang Q, Zhang W and Li L: Tumor suppressor genes associated with drug resistance in ovarian cancer (Review). Oncol Rep. 30:3–10. 2013.PubMed/NCBI

2 

Sorbe B, Graflund M, Nygren L, Horvath G, Swahn M, Boman K, Bangshöj R, Lood M and Malmström H: A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation. Int J Oncol. 40:773–781. 2012.

3 

Pello OM, De Pizzol M, Mirolo M, Soucek L, Zammataro L, Amabile A, Doni A, Nebuloni M, Swigart LB, Evan GI, Mantovani A and Locati M: Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. Blood. 119:411–421. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Okada M, Saio M, Kito Y, Ohe N, Yano H, Yoshimura S, Iwama T and Takami T: Tumor-associated macrophage/microglia infiltration in human gliomas is correlated with MCP-3, but not MCP-1. Int J Oncol. 34:1621–1627. 2009.PubMed/NCBI

5 

Zhang T, Ma Z, Wang R, Wang Y, Wang S, Cheng Z, Xu H, Jin X, Li W and Wang X: Thrombin facilitates invasion of ovarian cancer along peritoneum by inducing monocyte differentiation toward tumor-associated macrophage-like cells. Cancer Immunol Immunother. 59:1097–1108. 2010. View Article : Google Scholar

6 

Wang X, Deavers M, Patenia R, Bassett RL Jr, Mueller P, Ma Q, Wang E and Freedman RS: Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Transl Med. 4:302006. View Article : Google Scholar : PubMed/NCBI

7 

Webb S: A decade after the genome, bioinformatics comes of age. Biotechniques. 51:157–161. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, Balakrishnan L, Marimuthu A, Banerjee S, Somanathan DS, Sebastian A, Rani S, Ray S, Harrys Kishore CJ, Kanth S, Ahmed M, Kashyap MK, Mohmood R, Ramachandra YL, Krishna V, Rahiman BA, Mohan S, Ranganathan P, Ramabadran S, Chaerkady R and Pandey A: Human Protein Reference Database - 2009 update. Nucleic Acids Res. 37(Database issue): D767–D772. 2009.PubMed/NCBI

9 

Adamcsek B, Palla G, Farkas IJ, Derényi I and Vicsek T: CFinder: locating cliques and overlapping modules in biological networks. Bioinformatics. 22:1021–1023. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Gao Y, Lu XC, Yang HY, Liu XF, Cao J and Fan L: The molecular mechanism of the anticancer effect of atorvastatin: DNA microarray and bioinformatic analyses. Int J Mol Med. 30:765–774. 2012.PubMed/NCBI

11 

Smoot ME, Ono K, Ruscheinski J, Wang PL and Ideker T: Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 27:431–432. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Bretz J, Garcia J, Huang X, Kang L, Zhang Y, Toellner KM and Chen-Kiang S: Noxa mediates p18INK4c cell-cycle control of homeostasis in B cells and plasma cell precursors. Blood. 117:2179–2188. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Dickson MA, Tap WD, Keohan ML, D’Angelo SP, Gounder MM, Antonescu CR, Landa J, Qin LX, Rathbone DD, Condy MM, Ustoyev Y, Crago AM, Singer S and Schwartz GK: Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma. J Clin Oncol. 31:2024–2028. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Kolupaeva V and Basilico C: Overexpression of cyclin E/CDK2 complexes overcomes FGF-induced cell cycle arrest in the presence of hypophosphorylated Rb proteins. Cell Cycle. 11:2557–2566. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Baydoun HH, Pancewicz J, Bai X and Nicot C: HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression. Mol Cancer. 9:3022010. View Article : Google Scholar : PubMed/NCBI

16 

Lim S and Kaldis P: Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development. 140:3079–3093. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Lin WR, Lai MW and Yeh CT: Cyclin-dependent kinase-associated protein phosphatase is overexpressed in alcohol-related hepatocellular carcinoma and influences xenograft tumor growth. Oncol Rep. 29:903–910. 2013.

18 

Choi YH and Yoo YH: Taxol-induced growth arrest and apoptosis is associated with the upregulation of the Cdk inhibitor, p21WAF1/CIP1, in human breast cancer cells. Oncol Rep. 28:2163–2169. 2012.PubMed/NCBI

19 

Nair BC, Vallabhaneni S, Tekmal RR and Vadlamudi RK: Roscovitine confers tumor suppressive effect on therapy-resistant breast tumor cells. Breast Cancer Res. 13:R802011. View Article : Google Scholar : PubMed/NCBI

20 

Shin JS, Hong SW, Lee SL, Kim TH, Park IC, An SK, Lee WK, Lim JS, Kim KI, Yang Y, Lee SS, Jin DH and Lee MS: Serum starvation induces G1 arrest through suppression of Skp2-CDK2 and CDK4 in SK-OV-3 cells. Int J Oncol. 32:435–439. 2008.PubMed/NCBI

21 

Freedman RS, Ma Q, Wang E, Gallardo ST, Gordon IO, Shin JW, Jin P, Stroncek D and Marincola FM: Migration deficit in monocyte-macrophages in human ovarian cancer. Cancer Immunol Immunother. 57:635–645. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Pollard JW: Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 4:71–78. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Yip P, Chen TH, Seshaiah P, Stephen LL, Michael-Ballard KL, Mapes JP, Mansfield BC and Bertenshaw GP: Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers. PLoS One. 6:e295332011. View Article : Google Scholar : PubMed/NCBI

24 

Novitskiy SV, Ryzhov S, Zaynagetdinov R, Goldstein AE, Huang Y, Tikhomirov OY, Blackburn MR, Biaggioni I, Carbone DP, Feoktistov I and Dikov MM: Adenosine receptors in regulation of dendritic cell differentiation and function. Blood. 112:1822–1831. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar

26 

Saccani A, Schioppa T, Porta C, Biswas SK, Nebuloni M, Vago L, Bottazzi B, Colombo MP, Mantovani A and Sica A: p50 nuclear factor-κB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res. 66:11432–11440. 2006.

27 

Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L and Zou W: Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 10:942–949. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, Brumlik M, Cheng P, Curiel T, Myers L, Lackner A, Alvarez X, Ochoa A, Chen L and Zou W: B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med. 203:871–881. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Alon U: Biological networks: the tinkerer as an engineer. Science. 301:1866–1867. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Ravasz E and Barabási AL: Hierarchical organization in complex networks. Phys Rev E Stat Nonlin Soft Matter Phys. 67:0261122003. View Article : Google Scholar : PubMed/NCBI

31 

Hartwell LH, Hopfield JJ, Leibler S and Murray AW: From molecular to modular cell biology. Nature. 402:C47–C52. 1999. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Ma B, Li L, Jin Y, Ben W, Zhang D, Jiang K, Feng S, Huang L, Zheng J, Zheng J, et al: CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages. Oncol Rep 31: 2759-2768, 2014.
APA
Yang, Y., Ma, B., Li, L., Jin, Y., Ben, W., Zhang, D. ... Zheng, J. (2014). CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages. Oncology Reports, 31, 2759-2768. https://doi.org/10.3892/or.2014.3127
MLA
Yang, Y., Ma, B., Li, L., Jin, Y., Ben, W., Zhang, D., Jiang, K., Feng, S., Huang, L., Zheng, J."CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages". Oncology Reports 31.6 (2014): 2759-2768.
Chicago
Yang, Y., Ma, B., Li, L., Jin, Y., Ben, W., Zhang, D., Jiang, K., Feng, S., Huang, L., Zheng, J."CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages". Oncology Reports 31, no. 6 (2014): 2759-2768. https://doi.org/10.3892/or.2014.3127
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Ma B, Li L, Jin Y, Ben W, Zhang D, Jiang K, Feng S, Huang L, Zheng J, Zheng J, et al: CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages. Oncol Rep 31: 2759-2768, 2014.
APA
Yang, Y., Ma, B., Li, L., Jin, Y., Ben, W., Zhang, D. ... Zheng, J. (2014). CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages. Oncology Reports, 31, 2759-2768. https://doi.org/10.3892/or.2014.3127
MLA
Yang, Y., Ma, B., Li, L., Jin, Y., Ben, W., Zhang, D., Jiang, K., Feng, S., Huang, L., Zheng, J."CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages". Oncology Reports 31.6 (2014): 2759-2768.
Chicago
Yang, Y., Ma, B., Li, L., Jin, Y., Ben, W., Zhang, D., Jiang, K., Feng, S., Huang, L., Zheng, J."CDK2 and CDK4 play important roles in promoting the proliferation of SKOV3 ovarian carcinoma cells induced by tumor-associated macrophages". Oncology Reports 31, no. 6 (2014): 2759-2768. https://doi.org/10.3892/or.2014.3127
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