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Home / Equine Research Bank / Vet Res / BAG3 protects bovine papillomavirus type 1-transformed equin...
Veterinary research2013; 44(1); 61; doi: 10.1186/1297-9716-44-61

BAG3 protects bovine papillomavirus type 1-transformed equine fibroblasts against pro-death signals.

Abstract: In human cancer cells, BAG3 protein is known to sustain cell survival. Here, for the first time, we demonstrate the expression of BAG3 protein both in equine sarcoids in vivo and in EqS04b cells, a sarcoid-derived fully transformed cell line harbouring bovine papilloma virus (BPV)-1 genome. Evidence of a possible involvement of BAG3 in equine sarcoid carcinogenesis was obtained by immunohistochemistry analysis of tumour samples. We found that most tumour samples stained positive for BAG3, even though to a different grade, while normal dermal fibroblasts from healthy horses displayed very weak staining pattern for BAG3 expression. By siRNA technology, we demonstrate in EqS04b the role of BAG3 in counteracting basal as well as chemical-triggered pro-death signals. BAG3 down-modulation was indeed shown to promote cell death and cell cycle arrest in G0/G1. In addition, we found that BAG3 silencing sensitized EqS04b cells to phenethylisothiocyanate (PEITC), a promising cancer chemopreventive/chemotherapeutic agent present in edible cruciferous vegetables. Notably, such a pro-survival role of BAG3 was less marked in E. Derm cells, an equine BPV-negative fibroblast cell line taken as a normal counterpart. Altogether our findings might suggest a mutual cooperation between BAG3 and viral oncoproteins to sustain cell survival.
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Publication Date: 2013-07-22 PubMed ID: 23876161PubMed Central: PMC3729419DOI: 10.1186/1297-9716-44-61Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the role of BAG3 protein in protecting horse cells, transformed by bovine papillomavirus type 1, against signals that induce cell death. The outcome suggests that BAG3 protein helps these virus-transformed cells survive and could potentially cooperate with viral cancer-causing proteins for cell survival.

Background of the Research

  • Previous studies established that the BAG3 protein helps human cancer cells survive.
  • In this study, the researchers for the first time observed the expression of BAG3 protein in ‘sarcoids’ (a type of skin tumor) in horses, and in EqS04b cells, a cell line derived from horse sarcoids that contain bovine papillomavirus 1 (BPV-1) virus DNA.

Research Methodology

  • An immunohistochemical method was used to analyse tumour samples. Most of the tumor samples showed positive staining for BAG3, indicating the presence of the protein, while healthy cells showed a much weaker staining pattern.
  • The researchers used siRNA technology, a method used to silence gene expression, to diminish the role of BAG3 in the EqS04b cells.

Key Findings

  • Reducing BAG3 expression in the cells led to increased cell death and caused the cells to stop progressing through the cell cycle (cell cycle arrest at phase G0/G1).
  • Additionally, silencing BAG3 made EqS04b cells more sensitive to phenethylisothiocyanate (PEITC), which is a compound found in vegetables like broccoli and cabbage that has been heralded for its cancer prevention and treatment properties.
  • The pro-survival effect of BAG3 was less significant in E. Derm cells, a line of healthy horse cells that don’t contain the BPV virus, indicating that the virus may play a role in BAG3’s protective effect.

Conclusions and Implications

  • The findings suggest that there might be a collective effort between BAG3 and virus-induced cancer proteins to maintain cell survival.
  • This insight enhances the understanding of how cells transformed by BPV-1 manage to survive and possibly pave the way for developing new therapeutic interventions.

Cite This Article

APA
Cotugno R, Gallotta D, d'Avenia M, Corteggio A, Altamura G, Roperto F, Belisario MA, Borzacchiello G. (2013). BAG3 protects bovine papillomavirus type 1-transformed equine fibroblasts against pro-death signals. Vet Res, 44(1), 61. https://doi.org/10.1186/1297-9716-44-61

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 44
Issue: 1
Pages: 61

Researcher Affiliations

Cotugno, Roberta
  • Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n,132, 84084, Fisciano, Salerno, Italy. mabelisa@unisa.it.
Gallotta, Dario
    d'Avenia, Morena
      Corteggio, Annunziata
        Altamura, Gennaro
          Roperto, Franco
            Belisario, Maria Antonietta
              Borzacchiello, Giuseppe

                MeSH Terms

                • Animals
                • Apoptosis
                • Apoptosis Regulatory Proteins / metabolism
                • Bovine papillomavirus 1 / genetics
                • Bovine papillomavirus 1 / physiology
                • Carcinogenesis / pathology
                • Cell Cycle
                • Cell Line, Transformed
                • Cell Line, Tumor
                • Gene Silencing
                • Horse Diseases / pathology
                • Horse Diseases / virology
                • Horses
                • Humans
                • RNA, Small Interfering / metabolism
                • Skin Neoplasms / metabolism
                • Skin Neoplasms / veterinary
                • Skin Neoplasms / virology

                References

                This article includes 34 references
                1. Borzacchiello G, Corteggio A. Equine Sarcoid: state of the art. Ippologia 2009;20:7–14.
                2. Pilsworth RC, Knottenbelt D. Equine sarcoid. Equine Vet Educ 2007;19:260–262.
                  doi: 10.2746/095777307X209194google scholar: lookup
                3. Nasir L, Campo MS. Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids.. Vet Dermatol 2008 Oct;19(5):243-54.
                  doi: 10.1111/j.1365-3164.2008.00683.xpubmed: 18927950google scholar: lookup
                4. Venuti A, Paolini F, Nasir L, Corteggio A, Roperto S, Campo MS, Borzacchiello G. Papillomavirus E5: the smallest oncoprotein with many functions.. Mol Cancer 2011 Nov 11;10:140.
                  doi: 10.1186/1476-4598-10-140pmc: PMC3248866pubmed: 22078316google scholar: lookup
                5. Borzacchiello G, Russo V, Della Salda L, Roperto S, Roperto F. Expression of platelet-derived growth factor-beta receptor and bovine papillomavirus E5 and E7 oncoproteins in equine sarcoid.. J Comp Pathol 2008 Nov;139(4):231-7.
                  doi: 10.1016/j.jcpa.2008.07.006pubmed: 18814884google scholar: lookup
                6. Brandt S, Tober R, Corteggio A, Burger S, Sabitzer S, Walter I, Kainzbauer C, Steinborn R, Nasir L, Borzacchiello G. BPV-1 infection is not confined to the dermis but also involves the epidermis of equine sarcoids.. Vet Microbiol 2011 May 12;150(1-2):35-40.
                  doi: 10.1016/j.vetmic.2010.12.021pubmed: 21242040google scholar: lookup
                7. Handke W, Luig C, Popovic B, Krmpotic A, Jonjic S, Brune W. Viral inhibition of BAK promotes murine cytomegalovirus dissemination to salivary glands.. J Virol 2013 Mar;87(6):3592-6.
                  doi: 10.1128/JVI.02657-12pmc: PMC3592122pubmed: 23302869google scholar: lookup
                8. Rosati A, Ammirante M, Gentilella A, Basile A, Festa M, Pascale M, Marzullo L, Belisario MA, Tosco A, Franceschelli S, Moltedo O, Pagliuca G, Lerose R, Turco MC. Apoptosis inhibition in cancer cells: a novel molecular pathway that involves BAG3 protein.. Int J Biochem Cell Biol 2007;39(7-8):1337-42.
                  doi: 10.1016/j.biocel.2007.03.007pubmed: 17493862google scholar: lookup
                9. Ammirante M, Rosati A, Arra C, Basile A, Falco A, Festa M, Pascale M, d'Avenia M, Marzullo L, Belisario MA, De Marco M, Barbieri A, Giudice A, Chiappetta G, Vuttariello E, Monaco M, Bonelli P, Salvatore G, Di Benedetto M, Deshmane SL, Khalili K, Turco MC, Leone A. IKK{gamma} protein is a target of BAG3 regulatory activity in human tumor growth.. Proc Natl Acad Sci U S A 2010 Apr 20;107(16):7497-502.
                  doi: 10.1073/pnas.0907696107pmc: PMC2867736pubmed: 20368414google scholar: lookup
                10. Carra S. The stress-inducible HspB8-Bag3 complex induces the eIF2alpha kinase pathway: implications for protein quality control and viral factory degradation?. Autophagy 2009 Apr;5(3):428-9.
                  doi: 10.4161/auto.5.3.7894pubmed: 19202352google scholar: lookup
                11. Wang HQ, Meng X, Liu BQ, Li C, Gao YY, Niu XF, Li N, Guan Y, Du ZX. Involvement of JNK and NF-κB pathways in lipopolysaccharide (LPS)-induced BAG3 expression in human monocytic cells.. Exp Cell Res 2012 Jan 1;318(1):16-24.
                  doi: 10.1016/j.yexcr.2011.10.005pubmed: 22020323google scholar: lookup
                12. Rosati A, Leone A, Del Valle L, Amini S, Khalili K, Turco MC. Evidence for BAG3 modulation of HIV-1 gene transcription.. J Cell Physiol 2007 Mar;210(3):676-83.
                  doi: 10.1002/jcp.20865pmc: PMC2670777pubmed: 17187345google scholar: lookup
                13. Rosati A, Khalili K, Deshmane SL, Radhakrishnan S, Pascale M, Turco MC, Marzullo L. BAG3 protein regulates caspase-3 activation in HIV-1-infected human primary microglial cells.. J Cell Physiol 2009 Feb;218(2):264-7.
                  doi: 10.1002/jcp.21604pmc: PMC4503248pubmed: 18821563google scholar: lookup
                14. Kyratsous CA, Silverstein SJ. BAG3, a host cochaperone, facilitates varicella-zoster virus replication.. J Virol 2007 Jul;81(14):7491-503.
                  doi: 10.1128/JVI.00442-07pmc: PMC1933350pubmed: 17475647google scholar: lookup
                15. Young P, Anderton E, Paschos K, White R, Allday MJ. Epstein-Barr virus nuclear antigen (EBNA) 3A induces the expression of and interacts with a subset of chaperones and co-chaperones.. J Gen Virol 2008 Apr;89(Pt 4):866-877.
                  doi: 10.1099/vir.0.83414-0pmc: PMC2885026pubmed: 18343826google scholar: lookup
                16. Borzacchiello G, Russo V, Gentile F, Roperto F, Venuti A, Nitsch L, Campo MS, Roperto S. Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor beta receptor in naturally occurring bovine urinary bladder tumours.. Oncogene 2006 Feb 23;25(8):1251-60.
                  doi: 10.1038/sj.onc.1209152pubmed: 16205631google scholar: lookup
                17. Yuan ZQ, Gault EA, Gobeil P, Nixon C, Campo MS, Nasir L. Establishment and characterization of equine fibroblast cell lines transformed in vivo and in vitro by BPV-1: model systems for equine sarcoids.. Virology 2008 Apr 10;373(2):352-61.
                  doi: 10.1016/j.virol.2007.11.037pubmed: 18191170google scholar: lookup
                18. Altschul SF, Wootton JC, Gertz EM, Agarwala R, Morgulis A, Schäffer AA, Yu YK. Protein database searches using compositionally adjusted substitution matrices.. FEBS J 2005 Oct;272(20):5101-9.
                  doi: 10.1111/j.1742-4658.2005.04945.xpmc: PMC1343503pubmed: 16218944google scholar: lookup
                19. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry.. J Immunol Methods 1991 Jun 3;139(2):271-9.
                  doi: 10.1016/0022-1759(91)90198-Opubmed: 1710634google scholar: lookup
                20. Franceschelli S, Rosati A, Lerose R, De Nicola S, Turco MC, Pascale M. Bag3 gene expression is regulated by heat shock factor 1.. J Cell Physiol 2008 Jun;215(3):575-7.
                  doi: 10.1002/jcp.21397pubmed: 18286539google scholar: lookup
                21. Baldwin EL, Osheroff N. Etoposide, topoisomerase II and cancer.. Curr Med Chem Anticancer Agents 2005 Jul;5(4):363-72.
                  doi: 10.2174/1568011054222364pubmed: 16101488google scholar: lookup
                22. Dai Y, Dent P, Grant S. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes mitochondrial dysfunction and apoptosis induced by 7-hydroxystaurosporine and mitogen-activated protein kinase kinase inhibitors in human leukemia cells that ectopically express Bcl-2 and Bcl-xL.. Mol Pharmacol 2003 Dec;64(6):1402-9.
                  doi: 10.1124/mol.64.6.1402pubmed: 14645670google scholar: lookup
                23. Gupta P, Srivastava SK. Antitumor activity of phenethyl isothiocyanate in HER2-positive breast cancer models.. BMC Med 2012 Jul 24;10:80.
                  doi: 10.1186/1741-7015-10-80pmc: PMC3412708pubmed: 22824293google scholar: lookup
                24. Mi L, Gan N, Cheema A, Dakshanamurthy S, Wang X, Yang DCH, Chung FL. Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes.. J Biol Chem 2009 Jun 19;284(25):17039-17051.
                  doi: 10.1074/jbc.M901789200pmc: PMC2719342pubmed: 19339240google scholar: lookup
                25. d'Avenia M, Rosati A, Belisario MA, Torino M, Torino G, Turco MC, Pascale M. The expression of the pro-apoptotic gene Air is inducible in human pancreatic adenocarcinoma cells.. J Cell Physiol 2011 Sep;226(9):2207-12.
                  doi: 10.1002/jcp.22736pubmed: 21437899google scholar: lookup
                26. Rosati A, Graziano V, De Laurenzi V, Pascale M, Turco MC. BAG3: a multifaceted protein that regulates major cell pathways.. Cell Death Dis 2011 Apr 7;2(4):e141.
                  doi: 10.1038/cddis.2011.24pmc: PMC3122056pubmed: 21472004google scholar: lookup
                27. Gerhauser C. Cancer chemoprevention and nutriepigenetics: state of the art and future challenges.. Top Curr Chem 2013;329:73-132.
                  pubmed: 22955508doi: 10.1007/128_2012_360google scholar: lookup
                28. Zhu H, Liu P, Li J. BAG3: a new therapeutic target of human cancers?. Histol Histopathol 2012 Mar;27(3):257-61.
                  pubmed: 22237703doi: 10.14670/hh-27.257google scholar: lookup
                29. Kim HR, Lee MW, Kim DS, Jo HY, Lee SH, Chueh HW, Jung HL, Yoo KH, Sung KW, Koo HH. Etoposide sensitizes neuroblastoma cells expressing caspase 8 to TRAIL.. Cell Biol Int Rep (2010) 2012 Jun 21;19(1):e00017.
                  pmc: PMC3475444pubmed: 23124518doi: 10.1042/cbr20110008google scholar: lookup
                30. Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L. Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53.. Vet Res 2012 Dec 4;43(1):81.
                  doi: 10.1186/1297-9716-43-81pmc: PMC3557224pubmed: 23210796google scholar: lookup
                31. Romano MF, Festa M, Pagliuca G, Lerose R, Bisogni R, Chiurazzi F, Storti G, Volpe S, Venuta S, Turco MC, Leone A. BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis.. Cell Death Differ 2003 Mar;10(3):383-5.
                  doi: 10.1038/sj.cdd.4401167pubmed: 12700638google scholar: lookup
                32. Iwasaki M, Homma S, Hishiya A, Dolezal SJ, Reed JC, Takayama S. BAG3 regulates motility and adhesion of epithelial cancer cells.. Cancer Res 2007 Nov 1;67(21):10252-9.
                  doi: 10.1158/0008-5472.CAN-07-0618pubmed: 17974966google scholar: lookup
                33. Iwasaki M, Tanaka R, Hishiya A, Homma S, Reed JC, Takayama S. BAG3 directly associates with guanine nucleotide exchange factor of Rap1, PDZGEF2, and regulates cell adhesion.. Biochem Biophys Res Commun 2010 Sep 24;400(3):413-8.
                  doi: 10.1016/j.bbrc.2010.08.092pmc: PMC2954587pubmed: 20800573google scholar: lookup
                34. Chiappetta G, Basile A, Arra C, Califano D, Pasquinelli R, Barbieri A, De Simone V, Rea D, Giudice A, Pezzullo L, De Laurenzi V, Botti G, Losito S, Conforti D, Turco MC. BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein.. J Clin Endocrinol Metab 2012 Jan;97(1):E115-20.
                  doi: 10.1210/jc.2011-0484pubmed: 22072743google scholar: lookup

                Citations

                This article has been cited 4 times.
                1. De Marco M, Falco A, Iaccarino R, Raffone A, Mollo A, Guida M, Rosati A, Chetta M, Genovese G, De Caro F, Capunzo M, Turco MC, Uversky VN, Marzullo L. An emerging role for BAG3 in gynaecological malignancies.. Br J Cancer 2021 Sep;125(6):789-797.
                  doi: 10.1038/s41416-021-01446-2pubmed: 34099896google scholar: lookup
                2. Martano M, Altamura G, Power K, Restucci B, Carella F, Borzacchiello G, Maiolino P. Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study.. Pathogens 2020 Jan 14;9(1).
                  doi: 10.3390/pathogens9010058pubmed: 31947661google scholar: lookup
                3. Liang J, Sagum CA, Bedford MT, Sidhu SS, Sudol M, Han Z, Harty RN. Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress.. PLoS Pathog 2017 Jan;13(1):e1006132.
                  doi: 10.1371/journal.ppat.1006132pubmed: 28076420google scholar: lookup
                4. Cotugno R, Basile A, Romano E, Gallotta D, Belisario MA. BAG3 down-modulation sensitizes HPV18(+) HeLa cells to PEITC-induced apoptosis and restores p53.. Cancer Lett 2014 Nov 28;354(2):263-71.
                  doi: 10.1016/j.canlet.2014.08.022pubmed: 25175321google scholar: lookup
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