FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Pathogens / Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α...
Pathogens (Basel, Switzerland)2020; 9(1); 58; doi: 10.3390/pathogens9010058

Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study.

Abstract: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well known that delta bovine papillomaviruses are their causative agents. We have recently shown the presence in equine sarcoids of abnormal vessel structures, which could cause a hypoxic condition. The aim of this study was to analyze the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in a subset of BPV positive equine sarcoids and explore the relationship with vascular endothelial growth factor (VEGF) expression. Results: 80% of equine sarcoids showed strong cytoplasmic staining in >60% of neoplastic fibroblasts, while 20% of samples showed a moderate cytoplasmic staining in 40-60% of neoplastic fibroblasts for HIF-1α. Results of Western blotting (WB) were consistent with immunohistochemistry (IHC). Moreover, a positive correlation between HIF-1α and VEGF expression (r = 0.60, < 0.01) was observed. Conclusions: we have shown that HIF-1α was strongly expressed in equine sarcoid. The upregulation of HIF-1α has been described in numerous tumors and can be modulated by many proteins encoded by transforming viruses. Thus, it is also possible that BPV could have a relevant role in HIF-1α pathway regulation, contributing to the development of equine sarcoids by promoting HIF-1α/VEGF mediated tumor angiogenesis.
Get Full Text
Publication Date: 2020-01-14 PubMed ID: 31947661PubMed Central: PMC7168668DOI: 10.3390/pathogens9010058Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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.

This research studied the expression of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in equine sarcoids, common skin tumors in horses, and its relationship with vascular endothelial growth factor (VEGF), with results showing a significant correlation and suggesting that the factor could play a key role in tumor development.

Objective of the Study

  • The main aim of this study was to analyze the expression of the protein Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in a subset of equine sarcoids. These sarcoids, or skin tumors, are highly prevalent in the equine population and are often caused by delta bovine papillomaviruses.
  • The research further sought to assess the relationship between HIF-1α and vascular endothelial growth factor (VEGF) expression in these sarcoids.

Methodology and Results

  • The researchers used both Immunohistochemistry (IHC) and Western blotting (WB) for their analysis. These are common methods for detecting specific proteins in tissue samples.
  • The researchers found significant expression of HIF-1α in the sarcoids. In 80% of the samples, strong cytoplasmic staining for HIF-1α was noted in more than 60% of the tumor fibroblasts. 20% of the samples also showed moderate staining, suggesting some level of HIF-1α expression.
  • The results of the Western blotting experiment correlated with the findings from the immunohistochemistry, adding weight to the findings.
  • Furthermore, a significant positive correlation between HIF-1α and VEGF expression was observed. This suggests a link between these two factors in the development of equine sarcoids.

Conclusion

  • The study’s findings show that HIF-1α is strongly expressed in equine sarcoids. This conclusion is supported by the results of the immunohistochemistry and Western blotting investigations.
  • The correlation between HIF-1α and VEGF suggests that HIF-1α could potentially play a role in the tumor development process, particularly in forming new blood vessels, a process known as angiogenesis.
  • The researchers propose the theory that delta bovine papillomaviruses, known causative agents of these tumors, could influence the regulation of the HIF-1α pathway, therefore contributing to tumor angiogenesis and the formation of equine sarcoids.

Cite This Article

APA
(2020). Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study. Pathogens, 9(1), 58. https://doi.org/10.3390/pathogens9010058

Publication

Pathogens (Basel, Switzerland)
ISSN: 2076-0817
NlmUniqueID: 101596317
Country: Switzerland
Language: English
Volume: 9
Issue: 1
PII: 58

Researcher Affiliations

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 76 references
  1. Pascoe RR, Summers PM. Clinical Survey of Tumours and Tumor Like Lesions in Horses in Southeast.. Equ. Vet. J. 1981;13:325–329.
  2. Ragland WL, Keown GH, Spencer GR. Equine Sarcoid.. Equ. Vet. J. 1970;2:2–11.
    doi: 10.1111/j.2042-3306.1970.tb04145.xgoogle 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. Borzacchiello G, Corteggio A. Equine Sarcoid: State of the art.. Ippologia 2009;20:7–14.
  5. Berruex F, Gerber V, Wohlfender FD, Burger D, Koch C. Clinical course of sarcoids in 61 Franches-Montagnes horses over a 5-7 year period.. Vet Q 2016 Dec;36(4):189-196.
    doi: 10.1080/01652176.2016.1204483pubmed: 27327513google scholar: lookup
  6. Nasir L, Brandt S. Papillomavirus associated diseases of the horse.. Vet Microbiol 2013 Nov 29;167(1-2):159-67.
    doi: 10.1016/j.vetmic.2013.08.003pubmed: 24016387google scholar: lookup
  7. Angelos JA, Marti E, Lazary S, Carmichael LE. Characterization of BPV-like DNA in equine sarcoids.. Arch Virol 1991;119(1-2):95-109.
    doi: 10.1007/BF01314326pubmed: 1650553google scholar: lookup
  8. Otten N, von Tscharner C, Lazary S, Antczak DF, Gerber H. DNA of bovine papillomavirus type 1 and 2 in equine sarcoids: PCR detection and direct sequencing.. Arch Virol 1993;132(1-2):121-31.
    doi: 10.1007/BF01309847pubmed: 8394687google scholar: lookup
  9. Bergvall KE. Sarcoids.. Vet Clin North Am Equine Pract 2013 Dec;29(3):657-71.
    doi: 10.1016/j.cveq.2013.09.002pubmed: 24267682google scholar: lookup
  10. Borzacchiello G, Roperto F. Bovine papillomaviruses, papillomas and cancer in cattle.. Vet Res 2008 Sep-Oct;39(5):45.
    doi: 10.1051/vetres:2008022pubmed: 18479666google scholar: lookup
  11. Campo MS. Animal models of papillomavirus pathogenesis.. Virus Res 2002 Nov;89(2):249-61.
    doi: 10.1016/S0168-1702(02)00193-4pubmed: 12445664google scholar: lookup
  12. Carr EA, Théon AP, Madewell BR, Hitchcock ME, Schlegel R, Schiller JT. Expression of a transforming gene (E5) of bovine papillomavirus in sarcoids obtained from horses.. Am J Vet Res 2001 Aug;62(8):1212-7.
    doi: 10.2460/ajvr.2001.62.1212pubmed: 11497440google scholar: lookup
  13. Martens A, De Moor A, Ducatelle R. PCR detection of bovine papilloma virus DNA in superficial swabs and scrapings from equine sarcoids.. Vet J 2001 May;161(3):280-6.
    doi: 10.1053/tvjl.2000.0524pubmed: 11352485google scholar: lookup
  14. Martens A, De Moor A, Vlaminck L, Pille F, Steenhaut M. Evaluation of excision, cryosurgery and local BCG vaccination for the treatment of equine sarcoids.. Vet Rec 2001 Dec 1;149(22):665-9.
    doi: 10.1136/vr.149.22.665pubmed: 11765322google scholar: lookup
  15. Brandt S, Haralambus R, Schoster A, Kirnbauer R, Stanek C. Peripheral blood mononuclear cells represent a reservoir of bovine papillomavirus DNA in sarcoid-affected equines.. J Gen Virol 2008 Jun;89(Pt 6):1390-1395.
    doi: 10.1099/vir.0.83568-0pubmed: 18474554google scholar: lookup
  16. 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
  17. Wilson AD, Armstrong ELR, Gofton RG, Mason J, De Toit N, Day MJ. Characterisation of early and late bovine papillomavirus protein expression in equine sarcoids.. Vet Microbiol 2013 Mar 23;162(2-4):369-380.
    doi: 10.1016/j.vetmic.2012.10.010pubmed: 23123175google scholar: lookup
  18. Chambers G, Ellsmore VA, O'Brien PM, Reid SWJ, Love S, Campo MS, Nasir L. Association of bovine papillomavirus with the equine sarcoid.. J Gen Virol 2003 May;84(Pt 5):1055-1062.
    doi: 10.1099/vir.0.18947-0pubmed: 12692268google scholar: lookup
  19. Nasir L, Reid SW. Bovine papillomaviral gene expression in equine sarcoid tumours.. Virus Res 1999 Jun;61(2):171-5.
    doi: 10.1016/S0168-1702(99)00022-2pubmed: 10475087google scholar: lookup
  20. Araldi RP, Melo TC, Diniz N, Mazzuchelli-de-Souza J, Carvalho RF, Beçak W, Stocco RC. Bovine papillomavirus clastogenic effect analyzed in comet assay.. Biomed Res Int 2013;2013:630683.
    doi: 10.1155/2013/630683pmc: PMC3728492pubmed: 23956996google scholar: lookup
  21. Campos SR, Melo TC, Assaf S, Araldi RP, Mazzuchelli-de-Souza J, Sircili MP, Carvalho RF, Roperto F, Beçak W, Stocco RC. Chromosome aberrations in cells infected with bovine papillomavirus: comparing cutaneous papilloma, esophagus papilloma, and urinary bladder lesion cells.. ISRN Oncol 2013;2013:910849.
    doi: 10.1155/2013/910849pmc: PMC3835608pubmed: 24298391google scholar: lookup
  22. Melo TC, Araldi RP, Pessoa NS, de-Sá-Júnior PL, Carvalho RF, Beçak W, Stocco RC. Bos taurus papillomavirus activity in peripheral blood mononuclear cells: demonstrating a productive infection.. Genet Mol Res 2015 Dec 11;14(4):16712-27.
    doi: 10.4238/2015.December.11.19pubmed: 26681018google scholar: lookup
  23. Stocco dos Santos RC, Lindsey CJ, Ferraz OP, Pinto JR, Mirandola RS, Benesi FJ, Birgel EH, Pereira CA, Beçak W. Bovine papillomavirus transmission and chromosomal aberrations: an experimental model.. J Gen Virol 1998 Sep;79 ( Pt 9):2127-35.
    doi: 10.1099/0022-1317-79-9-2127pubmed: 9747721google scholar: lookup
  24. 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
  25. Cotugno R, Gallotta D, d'Avenia M, Corteggio A, Altamura G, Roperto F, Belisario MA, Borzacchiello G. BAG3 protects bovine papillomavirus type 1-transformed equine fibroblasts against pro-death signals.. Vet Res 2013 Jul 22;44(1):61.
    doi: 10.1186/1297-9716-44-61pmc: PMC3729419pubmed: 23876161google scholar: lookup
  26. Martano M, Corteggio A, Restucci B, De Biase ME, Borzacchiello G, Maiolino P. Extracellular matrix remodeling in equine sarcoid: an immunohistochemical and molecular study.. BMC Vet Res 2016 Feb 2;12:24.
    doi: 10.1186/s12917-016-0648-1pmc: PMC4736642pubmed: 26838095google scholar: lookup
  27. Martano M, Power K, Restucci B, Pagano I, Altamura G, Borzacchiello G, Maiolino P. Expression of vascular endothelial growth factor (VEGF) in equine sarcoid.. BMC Vet Res 2018 Sep 3;14(1):266.
    doi: 10.1186/s12917-018-1576-zpmc: PMC6122557pubmed: 30176852google scholar: lookup
  28. Folkman J. Role of angiogenesis in tumor growth and metastasis.. Semin Oncol 2002 Dec;29(6 Suppl 16):15-8.
    doi: 10.1053/sonc.2002.37263pubmed: 12516034google scholar: lookup
  29. Maiolino P, De Vico G, Restucci B. Expression of vascular endothelial growth factor in basal cell tumours and in squamous cell carcinomas of canine skin.. J Comp Pathol 2000 Aug-Oct;123(2-3):141-5.
    doi: 10.1053/jcpa.2000.0404pubmed: 11032667google scholar: lookup
  30. Maiolino P, Papparella S, Restucci B, De Vico G. Angiogenesis in squamous cell carcinomas of canine skin: an immunohistochemical and quantitative analysis.. J Comp Pathol 2001 Aug-Oct;125(2-3):117-21.
    doi: 10.1053/jcpa.2001.0485pubmed: 11578126google scholar: lookup
  31. Martano M, Maiolino P, Cataldi M, Restucci B. Evaluation of angiogenesis by morphometric analysis of blood vessels in dysplastic and neoplastic lesions of canine gingiva.. Vet Res Commun 2004 Aug;28 Suppl 1:299-301.
    doi: 10.1023/B:VERC.0000045431.82158.4epubmed: 15372982google scholar: lookup
  32. Martano M, Restucci B, Ceccarelli DM, Lo Muzio L, Maiolino P. Immunohistochemical expression of vascular endothelial growth factor in canine oral squamous cell carcinomas.. Oncol Lett 2016 Jan;11(1):399-404.
    doi: 10.3892/ol.2015.3847pmc: PMC4727185pubmed: 26870224google scholar: lookup
  33. Restucci B, De Vico G, Maiolino P. Evaluation of angiogenesis in canine mammary tumors by quantitative platelet endothelial cell adhesion molecule immunohistochemistry.. Vet Pathol 2000 Jul;37(4):297-301.
    doi: 10.1354/vp.37-4-297pubmed: 10896390google scholar: lookup
  34. Restucci B, Papparella S, Maiolino P, De Vico G. Expression of vascular endothelial growth factor in canine mammary tumors.. Vet Pathol 2002 Jul;39(4):488-93.
    doi: 10.1354/vp.39-4-488pubmed: 12126152google scholar: lookup
  35. Restucci B, Maiolino P, Paciello O, Martano M, De Vico G, Papparella S. Evaluation of angiogenesis in canine seminomas by quantitative immunohistochemistry.. J Comp Pathol 2003 May;128(4):252-9.
    doi: 10.1053/jcpa.2002.0630pubmed: 12834608google scholar: lookup
  36. Restucci B, Borzacchiello G, Maiolino P, Martano M, Paciello O, Papparella S. Expression of vascular endothelial growth factor receptor Flk-1 in canine mammary tumours.. J Comp Pathol 2004 Feb-Apr;130(2-3):99-104.
    doi: 10.1016/j.jcpa.2003.07.001pubmed: 15003465google scholar: lookup
  37. Restucci B, Martano M, Maiolino P. Expression of endothelin-1 and endothelin-1 receptor A in canine mammary tumours.. Res Vet Sci 2015 Jun;100:182-8.
    doi: 10.1016/j.rvsc.2015.03.008pubmed: 25816929google scholar: lookup
  38. Bárdos JI, Ashcroft M. Negative and positive regulation of HIF-1: a complex network.. Biochim Biophys Acta 2005 Jul 25;1755(2):107-20.
    doi: 10.1016/j.bbcan.2005.05.001pubmed: 15994012google scholar: lookup
  39. Brat DJ, Kaur B, Van Meir EG. Genetic modulation of hypoxia induced gene expression and angiogenesis: relevance to brain tumors.. Front Biosci 2003 Jan 1;8:d100-16.
    doi: 10.2741/942pubmed: 12456339google scholar: lookup
  40. Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress.. Mol Cell 2010 Oct 22;40(2):294-309.
    doi: 10.1016/j.molcel.2010.09.022pmc: PMC3143508pubmed: 20965423google scholar: lookup
  41. Shay JE, Celeste Simon M. Hypoxia-inducible factors: crosstalk between inflammation and metabolism.. Semin Cell Dev Biol 2012 Jun;23(4):389-94.
    doi: 10.1016/j.semcdb.2012.04.004pubmed: 22525300google scholar: lookup
  42. Weidemann A, Johnson RS. Biology of HIF-1alpha.. Cell Death Differ 2008 Apr;15(4):621-7.
    doi: 10.1038/cdd.2008.12pubmed: 18259201google scholar: lookup
  43. Aebersold DM, Burri P, Beer KT, Laissue J, Djonov V, Greiner RH, Semenza GL. Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer.. Cancer Res 2001 Apr 1;61(7):2911-6.
    pubmed: 11306467
  44. Beasley NJ, Leek R, Alam M, Turley H, Cox GJ, Gatter K, Millard P, Fuggle S, Harris AL. Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients.. Cancer Res 2002 May 1;62(9):2493-7.
    pubmed: 11980639
  45. Bos R, Zhong H, Hanrahan CF, Mommers EC, Semenza GL, Pinedo HM, Abeloff MD, Simons JW, van Diest PJ, van der Wall E. Levels of hypoxia-inducible factor-1 alpha during breast carcinogenesis.. J Natl Cancer Inst 2001 Feb 21;93(4):309-14.
    doi: 10.1093/jnci/93.4.309pubmed: 11181778google scholar: lookup
  46. Giatromanolaki A, Koukourakis MI, Sivridis E, Turley H, Talks K, Pezzella F, Gatter KC, Harris AL. Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival.. Br J Cancer 2001 Sep 14;85(6):881-90.
    doi: 10.1054/bjoc.2001.2018pmc: PMC2375073pubmed: 11556841google scholar: lookup
  47. Koukourakis MI, Giatromanolaki A, Sivridis E, Simopoulos C, Turley H, Talks K, Gatter KC, Harris AL. Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer.. Int J Radiat Oncol Biol Phys 2002 Aug 1;53(5):1192-202.
    doi: 10.1016/S0360-3016(02)02848-1pubmed: 12128120google scholar: lookup
  48. Kuwai T, Kitadai Y, Tanaka S, Onogawa S, Matsutani N, Kaio E, Ito M, Chayama K. Expression of hypoxia-inducible factor-1alpha is associated with tumor vascularization in human colorectal carcinoma.. Int J Cancer 2003 Jun 10;105(2):176-81.
    doi: 10.1002/ijc.11068pubmed: 12673675google scholar: lookup
  49. Sivridis E, Giatromanolaki A, Gatter KC, Harris AL, Koukourakis MI. Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma.. Cancer 2002 Sep 1;95(5):1055-63.
    doi: 10.1002/cncr.10774pubmed: 12209691google scholar: lookup
  50. Tuder RM, Chacon M, Alger L, Wang J, Taraseviciene-Stewart L, Kasahara Y, Cool CD, Bishop AE, Geraci M, Semenza GL, Yacoub M, Polak JM, Voelkel NF. Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis.. J Pathol 2001 Oct;195(3):367-74.
    doi: 10.1002/path.953pubmed: 11673836google scholar: lookup
  51. Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW, Semenza GL. Expression of hypoxia-inducible factor 1alpha in brain tumors: association with angiogenesis, invasion, and progression.. Cancer 2000 Jun 1;88(11):2606-18.
    doi: 10.1002/1097-0142(20000601)88:11<2606::AID-CNCR25>3.0.CO;2-Wpubmed: 10861440google scholar: lookup
  52. Talwar H, Bouhamdan M, Bauerfeld C, Talreja J, Aoidi R, Houde N, Charron J, Samavati L. MEK2 Negatively Regulates Lipopolysaccharide-Mediated IL-1β Production through HIF-1α Expression.. J Immunol 2019 Mar 15;202(6):1815-1825.
    doi: 10.4049/jimmunol.1801477pmc: PMC6401293pubmed: 30710049google scholar: lookup
  53. Knight M, Stanley S. HIF-1α as a central mediator of cellular resistance to intracellular pathogens.. Curr Opin Immunol 2019 Oct;60:111-116.
    doi: 10.1016/j.coi.2019.05.005pubmed: 31229914google scholar: lookup
  54. Sun R, Meng X, Pu Y, Sun F, Man Z, Zhang J, Yin L, Pu Y. Overexpression of HIF-1a could partially protect K562 cells from 1,4-benzoquinone induced toxicity by inhibiting ROS, apoptosis and enhancing glycolysis.. Toxicol In Vitro 2019 Mar;55:18-23.
    doi: 10.1016/j.tiv.2018.11.005pubmed: 30448556google scholar: lookup
  55. Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy.. Hypoxia (Auckl) 2015;3:83-92.
    doi: 10.2147/HP.S93413pmc: PMC5045092pubmed: 27774485google scholar: lookup
  56. Dunn T. Oxygen and cancer.. N C Med J 1997 Mar-Apr;58(2):140-3.
    pubmed: 9088144
  57. Semenza GL. Targeting HIF-1 for cancer therapy.. Nat Rev Cancer 2003 Oct;3(10):721-32.
    doi: 10.1038/nrc1187pubmed: 13130303google scholar: lookup
  58. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.. Oncogene 2010 Feb 4;29(5):625-34.
    doi: 10.1038/onc.2009.441pmc: PMC2969168pubmed: 19946328google scholar: lookup
  59. Kallio PJ, Wilson WJ, O'Brien S, Makino Y, Poellinger L. Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway.. J Biol Chem 1999 Mar 5;274(10):6519-25.
    doi: 10.1074/jbc.274.10.6519pubmed: 10037745google scholar: lookup
  60. Cao D, Hou M, Guan YS, Jiang M, Yang Y, Gou HF. Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications.. BMC Cancer 2009 Dec 10;9:432.
    doi: 10.1186/1471-2407-9-432pmc: PMC2797529pubmed: 20003271google scholar: lookup
  61. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor.. Endocr Rev 1997 Feb;18(1):4-25.
    doi: 10.1210/edrv.18.1.0287pubmed: 9034784google scholar: lookup
  62. Goel HL, Mercurio AM. VEGF targets the tumour cell.. Nat Rev Cancer 2013 Dec;13(12):871-82.
    doi: 10.1038/nrc3627pmc: PMC4011842pubmed: 24263190google scholar: lookup
  63. Liang X, Yang D, Hu J, Hao X, Gao J, Mao Z. Hypoxia inducible factor-alpha expression correlates with vascular endothelial growth factor-C expression and lymphangiogenesis/angiogenesis in oral squamous cell carcinoma.. Anticancer Res 2008 May-Jun;28(3A):1659-66.
    pubmed: 18630523
  64. Semenza GL. Molecular mechanisms mediating metastasis of hypoxic breast cancer cells.. Trends Mol Med 2012 Sep;18(9):534-43.
    doi: 10.1016/j.molmed.2012.08.001pmc: PMC3449282pubmed: 22921864google scholar: lookup
  65. Depping R, Jelkmann W, Kosyna FK. Nuclear-cytoplasmatic shuttling of proteins in control of cellular oxygen sensing.. J Mol Med (Berl) 2015 Jun;93(6):599-608.
    doi: 10.1007/s00109-015-1276-0pubmed: 25809665google scholar: lookup
  66. Baba Y, Nosho K, Shima K, Irahara N, Chan AT, Meyerhardt JA, Chung DC, Giovannucci EL, Fuchs CS, Ogino S. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers.. Am J Pathol 2010 May;176(5):2292-301.
    doi: 10.2353/ajpath.2010.090972pmc: PMC2861094pubmed: 20363910google scholar: lookup
  67. Shin JI, Lim HY, Kim HW, Seung BJ, Sur JH. Analysis of Hypoxia-Inducible Factor-1α Expression Relative to Other Key Factors in Malignant Canine Mammary Tumours.. J Comp Pathol 2015 Aug-Oct;153(2-3):101-10.
    doi: 10.1016/j.jcpa.2015.05.004pubmed: 26145724google scholar: lookup
  68. Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, Bucana CD, Semenza GL, Ellis LM. Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis, and vessel maturation.. J Natl Cancer Inst 2004 Jun 16;96(12):946-56.
    doi: 10.1093/jnci/djh168pubmed: 15199114google scholar: lookup
  69. Cuninghame S, Jackson R, Zehbe I. Hypoxia-inducible factor 1 and its role in viral carcinogenesis.. Virology 2014 May;456-457:370-83.
    doi: 10.1016/j.virol.2014.02.027pubmed: 24698149google scholar: lookup
  70. Li G, He L, Zhang E, Shi J, Zhang Q, Le AD, Zhou K, Tang X. Overexpression of human papillomavirus (HPV) type 16 oncoproteins promotes angiogenesis via enhancing HIF-1α and VEGF expression in non-small cell lung cancer cells.. Cancer Lett 2011 Dec 8;311(2):160-70.
    doi: 10.1016/j.canlet.2011.07.012pubmed: 21868151google scholar: lookup
  71. Nakamura M, Bodily JM, Beglin M, Kyo S, Inoue M, Laimins LA. Hypoxia-specific stabilization of HIF-1alpha by human papillomaviruses.. Virology 2009 May 10;387(2):442-8.
    doi: 10.1016/j.virol.2009.02.036pmc: PMC2674135pubmed: 19321184google scholar: lookup
  72. Bischof O, Nacerddine K, Dejean A. Human papillomavirus oncoprotein E7 targets the promyelocytic leukemia protein and circumvents cellular senescence via the Rb and p53 tumor suppressor pathways.. Mol Cell Biol 2005 Feb;25(3):1013-24.
    doi: 10.1128/MCB.25.3.1013-1024.2005pmc: PMC543993pubmed: 15657429google scholar: lookup
  73. Knuth J, Sharma SJ, Würdemann N, Holler C, Garvalov BK, Acker T, Wittekindt C, Wagner S, Klussmann JP. Hypoxia-inducible factor-1α activation in HPV-positive head and neck squamous cell carcinoma cell lines.. Oncotarget 2017 Oct 27;8(52):89681-89691.
    doi: 10.18632/oncotarget.20813pmc: PMC5685701pubmed: 29163780google scholar: lookup
  74. Araldi RP, Assaf SMR, Carvalho RF, Carvalho MACR, Souza JM, Magnelli RF, Módolo DG, Roperto FP, Stocco RC, Beçak W. Papillomaviruses: a systematic review.. Genet Mol Biol 2017 Jan-Mar;40(1):1-21.
    doi: 10.1590/1678-4685-gmb-2016-0128pmc: PMC5409773pubmed: 28212457google scholar: lookup
  75. Nagao A, Kobayashi M, Koyasu S, Chow CCT, Harada H. HIF-1-Dependent Reprogramming of Glucose Metabolic Pathway of Cancer Cells and Its Therapeutic Significance.. Int J Mol Sci 2019 Jan 9;20(2).
    doi: 10.3390/ijms20020238pmc: PMC6359724pubmed: 30634433google scholar: lookup
  76. Albadari N, Deng S, Li W. The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy.. Expert Opin Drug Discov 2019 Jul;14(7):667-682.
    doi: 10.1080/17460441.2019.1613370pmc: PMC6559821pubmed: 31070059google scholar: lookup

Citations

This article has been cited 2 times.
  1. Martano M, Altamura G, Power K, Liguori P, Restucci B, Borzacchiello G, Maiolino P. Beclin 1, LC3 and P62 Expression in Equine Sarcoids.. Animals (Basel) 2021 Dec 23;12(1).
    doi: 10.3390/ani12010020pubmed: 35011126google scholar: lookup
  2. Otto S, Michler JK, Dhein S, Mülling CKW. Development of a constant pressure perfused ex vivo model of the equine larynx.. PLoS One 2021;16(5):e0251530.
    doi: 10.1371/journal.pone.0251530pubmed: 34014952google scholar: lookup
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.