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REG gamma: a potential marker in breast cancer and effect on cell cycle and proliferation of breast cancer cell

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Abstract

To investigate the expression and significance of proteasomes reactivator REG gamma (γ) in breast cancer. First, we showed the expression of REGγ in breast cancer, metastatic lymph nodes and normal breast tissues. Meanwhile, we also analyzed the relationship between REGγ and estrogen receptor (ER), CerBb-2, lymph nodes metastasis and clinical stage of breast cancer. REGγ expression was determined by immunohistochemical staining and western blot. Secondly, we detected the expression of REGγ and REGγ-mRNA in human breast cancer cell lines (MDA-MB-231, MCF-7) and human breast ductal epithelial cell line (HBL-100) by western blot and real-time PCR. Finally, in order to identify effect of REGγ on breast cancer cell cycle and proliferation, we constructed recombinant plasmid of PcDNA3.1-REGγ and designed siRNA for REGγ in vitro. Cell cycle was assayed by flow cytometer (FCM), proliferation was measured by methyl thiazolyl tetrazolium (MTT). The results demonstrated abnormal high expression of REGγ in breast cancer and its metastatic lymph nodes. REGγ expression was related to breast cancer and its status of ER, CerBb-2 and lymph nodes metastasis. REGγ is one of the potential markers in breast cancer. REGγ could facilitate the growth of breast cancer cells.

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Abbreviations

ER:

Estrogen receptor

PCNA:

Proliferating cell nuclear antigen

siRNA RNA:

Interfere

FCS:

Foetal calf serum

MTT:

Methyl thiazolyl tetrazolium

FCM:

Flow cytometer

References

  1. Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996;65:801–47.

    Article  PubMed  CAS  Google Scholar 

  2. Lowe J, Stock D, Jap B, Zwickl P, et al. Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. Science. 1995;268:533–9.

    Article  PubMed  CAS  Google Scholar 

  3. Ahn K, Erlander M, Leturcq D, Peterson PA, et al. In vivo characterization of the proteasome regulator PA28. J Biol Chem. 1996;271:18237–42.

    Article  PubMed  CAS  Google Scholar 

  4. Soza A, Knuehl C, Groettrup M, Henklein P, et al. Expression and subcellular localization of mouse 20S proteasome activator complex PA28. FEBS Lett. 1997;413:27–34.

    Article  PubMed  CAS  Google Scholar 

  5. Wojcik C, Tanaka K, Paweletz N, Naab U, et al. Proteasome activator (PA28) subunits, α, β and γ (Ki antigen) in NT2 neuronal precursor cells and HeLa S3 cells. Eur J Cell Biol. 1998;77:151–60.

    PubMed  CAS  Google Scholar 

  6. Rechsteiner M, Realini C, Ustrell V. The proteasome activator 11S REG(PA28) and classIantigen presentation. Biochem J. 2000;345:1–15.

    Article  PubMed  CAS  Google Scholar 

  7. Luscher B, Eisenman RN. c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock. Mol Cell Biol. 1998;8:2504–12.

    Google Scholar 

  8. Salvat C, Aquaviva C, Jariel-Encontre I, et al. Are there multiple proteolytic pathways contributing to c-Fos, c-Jun and p53 protein degradation in vivo? Mol Biol Rep. 1999;26:45–51.

    Article  PubMed  CAS  Google Scholar 

  9. He H, Qi XM, Grossmann J, et al. c-Fos degradation by the proteasome. An early, Bcl-2-regulated step in apoptosis. J Biol Chem. 1998;273:25015–9.

    Article  PubMed  CAS  Google Scholar 

  10. Glotzer M, Murry AW, Kirschner MW. Cyclin is degraded by the ubiquitin pathway. Nature. 1991;349:132–8.

    Article  PubMed  CAS  Google Scholar 

  11. Moro A, Perea SE, Pantoja C, et al. IFNα2b induces apoptosis and proteasome-mediated degradation of p27Kip1 in a human lung cancer cell line. Oncol Rep. 2001;8:425–9.

    PubMed  CAS  Google Scholar 

  12. Machiels BM, Henfling ME, Broers JL, et al. Changes in immunocytochemical detectability of proteasome epitopes depending on cell growth and fixation conditions of lung cancer cell lines. Eur J Cell Biol. 1995;66:282–92.

    PubMed  CAS  Google Scholar 

  13. Kanayama H, Tanaka K, Aki M, et al. Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells. Cancer Res. 1991;51:6677–85.

    PubMed  CAS  Google Scholar 

  14. Fan XM, Wong BC, Wang WP, et al. Inhibition of proteasome function induced apoptosis in gastric cancer. Int J Cancer. 2001;93:481–8.

    Article  PubMed  CAS  Google Scholar 

  15. Bold RJ, Virudachalam S, McConkey DJ. Chemosensitization of pancreatic cancer by inhibition of the 26s proteasome. J Surg Res. 2001;100:11–7.

    Article  PubMed  CAS  Google Scholar 

  16. Tenev T, Marani M, McNeish I, et al. Pro-caspase-3 overexpression sensitizes ovarian cancer cells to proteasome inhibitors. Cell Death Differ. 2001;8:256–64.

    Article  PubMed  CAS  Google Scholar 

  17. Kumatori A, Tanaka K, Inamura N, et al. Abnormally high expression of proteasomes in human leukemic cells. Proc Natl Acad Sci USA. 1990;87:7071–5.

    Article  PubMed  CAS  Google Scholar 

  18. Murata S, Kawahara H, Tohma S, et al. Growth retardation in mice lacking the proteasome activator PA28γ. J Biol Chem. 1999;274:38211–5.

    Article  PubMed  CAS  Google Scholar 

  19. Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer. 2001;1:222–31.

    Article  PubMed  CAS  Google Scholar 

  20. Hung CF, Lu KC, Cheng TZ, et al. A novel siRNA validation system for functional screening and identification of effective RNAi probes in mammalian cells. Biochem Biophys Res Commun. 2006;346(3):707–20.

    Article  PubMed  CAS  Google Scholar 

  21. Masson P, Andersson O, Petersen UM, et al. Identification and characterization of a Drosophila nuclear proteasome regulator. A homolog of human 11 S REGγ(PA28γ). J Biol Chem. 2001;276:1383–90.

    Article  PubMed  CAS  Google Scholar 

  22. Gao X, Li J, Pratt G, et al. Purification procedures determine the proteasome activation properties of REG gamma (PA28 gamma). Arch Biochem Biophys. 2004;425:158–64.

    Article  PubMed  CAS  Google Scholar 

  23. Tomohisa O, Shin-Ichi T, Tsuyoshi O, et al. Abnormally high expression of proteasome activator-γin Thyroid neoplasm. J Clin Endocrinol Metab. 2003;88:1374–83.

    Article  Google Scholar 

  24. Chen X, Barton LF, Chi Y, et al. Ubiquitin-independent degradation of cell-cycle inhibitors by the REG gamma proteasome. Mol Cell. 2007;26:843–52.

    Article  PubMed  CAS  Google Scholar 

  25. Yi T, Baek JH, Kim HJ, et al. Trichostatin A-mediated upregulation of p21(WAF1) contributes to osteoclast apoptosis. Exp Mol Med. 2007;39:213–21.

    PubMed  CAS  Google Scholar 

  26. Lee CJ, Kim HT, et al. Ovarian expression of p53 and p21 apoptosis regulators in gamma-irradiated mice. Mol Reprod Dev. 2008;75:383–91.

    Article  PubMed  CAS  Google Scholar 

  27. Bianchi S, Paglierani M, Zampi G, et al. Prognostic value of proliferating cell nuclear antigen in lymph node-negative breast cancer patients. Cancer. 1993;72:120–5.

    Article  PubMed  CAS  Google Scholar 

  28. Clark GM, Sledge GW, Osborne CK, et al. Survival from first recurrence: relative importance of prognostic factors in 1015 breast cancer patients. J Clin Oncol. 1987;5:55–61.

    PubMed  CAS  Google Scholar 

  29. Thompson DA, Weigel RJ. Characterization of a gene that is inversely correlated with oestrogen receptor expression (ICERE-1) in breast carcinomas. Eur J Biochem. 1998;252:169–77.

    Article  PubMed  CAS  Google Scholar 

  30. Platet N, Prevostel C, Derocq D, et al. Breast cancer cell invasiveness: correlation with protein kinase C activity and differential regulation by phorbol ester in oestrogen receptor-positive and -negative cells. Int J Cancer. 1998;75:750–6.

    Article  PubMed  CAS  Google Scholar 

  31. Pluciennik E, Kusinska R, Potemski P, et al. WWOX—the FRA16D cancer gene: expression correlation with breast cancer progression and prognosis. Eur J Surg Oncol. 2006;32:153–7.

    Article  PubMed  CAS  Google Scholar 

  32. Tagliabue E, Menard S, Robertson JF, et al. c-erbB-2 expression in primary breast cancer. Int J Biol Markers. 1999;14:16–26.

    PubMed  CAS  Google Scholar 

  33. Shunqian J, Qimin Z. Oncomolecularbiology is the forefront of basic medical research. World Chin J Dig. 2002;10:678–80.

    Google Scholar 

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 30670811). The authors thank Jean-Francois RODIER for his generous help of modified article. The authors thank Prof. Shen Zhen Zhou (Tumor Hospital of Shanghai, China) for his generous gift of MDA-MB-231 cell line.

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Correspondence to Guosheng Ren.

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Wang, X., Tu, S., Tan, J. et al. REG gamma: a potential marker in breast cancer and effect on cell cycle and proliferation of breast cancer cell. Med Oncol 28, 31–41 (2011). https://doi.org/10.1007/s12032-010-9546-8

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  • DOI: https://doi.org/10.1007/s12032-010-9546-8

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