Expression of cell cycle associated proteins cyclin A, CDK-2, p27kip1 and p53 in equine sarcoids.
Abstract: Equine sarcoids are benign fibroblastic skin tumours affecting equids worldwide. Whilst the pathogenesis is not entirely understood, infection with Bovine Papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in the disease process, however the mechanism by which BPV infection contributes to sarcoid pathology is not clear. In this study, we show that the majority of sarcoids express the BPV-1 major transforming gene E6. Further, we demonstrate that sarcoid lesions are not associated with high levels of cellular proliferation as assessed by Ki67 expression or with expression of cell cycle regulators CDK-2, cyclin A and p27kip1. Our analysis of p53 shows that a subset of sarcoids are associated with abnormal cytoplasmic and nuclear expression of p53 and that the transactivation function of p53 is compromised in cells with cytoplasmic p53.
Publication Date: 2005-04-06 PubMed ID: 15808409DOI: 10.1016/j.canlet.2004.08.039Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers studied the expression of several proteins associated with the cell cycle in equine sarcoids, a type of benign skin tumor found in equids such as horses. The results suggest that most sarcoids express the E6 transforming gene from Bovine Papillomavirus Type 1, but do not show high levels of cell proliferation or expression of cell cycle regulators. Abnormal expression of the p53 protein was found in a subset of sarcoids.
Study Focus: Equine Sarcoids and BPV Infection
- Equine sarcoids are benign, or non-cancerous, skin tumors that affect equines around the world. The precise cause of these tumors is not completely understood.
- Bovine Papillomavirus (BPV) types 1 and 2 have been implicated as a primary factor in the development of these tumors, but the exact mechanism behind this is not clear.
E6 Transforming Gene and Cell Proliferation
- The study showed that the majority of sarcoids express the E6 transforming gene from BPV-1.
- Despite this, the researchers found that these lesions were not associated with high levels of cellular proliferation. Cellular proliferation refers to the process by which cells rapidly divide and grow, a major trait of cancerous tumors.
- High levels of expression of the cell cycle regulators cyclin A, CDK-2, and p27kip1 were not observed. These proteins play critical roles in regulating cell division and growth.
Abnormal p53 Expression
- P53 is a protein that helps to keep cells from growing and dividing too rapidly or in an uncontrolled way. It can prevent the formation of tumors and is often referred to as a tumor suppressor protein.
- Abnormal expression of p53 was found in certain sarcoids, with unusual cytoplasmic and nuclear expression patterns observed.
- This abnormal expression impairs p53’s transactivation function – its ability to activate the transcription of other genes. Transcription is the first step in gene expression, where a particular segment of DNA is copied into RNA.
Cite This Article
APA
Nixon C, Chambers G, Ellsmore V, Campo MS, Burr P, Argyle DJ, Reid SW, Nasir L.
(2005).
Expression of cell cycle associated proteins cyclin A, CDK-2, p27kip1 and p53 in equine sarcoids.
Cancer Lett, 221(2), 237-245.
https://doi.org/10.1016/j.canlet.2004.08.039 Publication
Researcher Affiliations
- Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, Scotland, UK.
MeSH Terms
- Animals
- Bovine papillomavirus 1 / pathogenicity
- CDC2-CDC28 Kinases / genetics
- CDC2-CDC28 Kinases / metabolism
- Cattle
- Cell Cycle Proteins / genetics
- Cell Cycle Proteins / metabolism
- Cell Proliferation
- Cyclin A / genetics
- Cyclin A / metabolism
- Cyclin-Dependent Kinase 2
- Cyclin-Dependent Kinase Inhibitor p27
- DNA, Viral / analysis
- DNA, Viral / genetics
- Fibroblasts / metabolism
- Fibroblasts / virology
- Gene Expression Regulation, Viral
- Horse Diseases / metabolism
- Horse Diseases / virology
- Horses
- Ki-67 Antigen / metabolism
- Oncogene Proteins, Viral / genetics
- Papillomavirus Infections / metabolism
- Papillomavirus Infections / veterinary
- Papillomavirus Infections / virology
- Skin Diseases / metabolism
- Skin Diseases / veterinary
- Skin Diseases / virology
- Transcriptional Activation
- Tumor Suppressor Protein p53 / genetics
- Tumor Suppressor Protein p53 / metabolism
- Tumor Suppressor Proteins / genetics
- Tumor Suppressor Proteins / metabolism
Citations
This article has been cited 8 times.- Tura G, Brunetti B, Brigandì E, Rinnovati R, Sarli G, Avallone G, Muscatello LV, La Ragione RM, Durham AE, Bacci B. Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids.. Vet Sci 2022 Sep 1;9(9).
- Thaiwong T, Sledge DG, Wise AG, Olstad K, Maes RK, Kiupel M. Malignant transformation of canine oral papillomavirus (CPV1)-associated papillomas in dogs: An emerging concern?. Papillomavirus Res 2018 Dec;6:83-89.
- 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.
- Jung JH, Yun M, Choo EJ, Kim SH, Jeong MS, Jung DB, Lee H, Kim EO, Kato N, Kim B, Srivastava SK, Kaihatsu K, Kim SH. A derivative of epigallocatechin-3-gallate induces apoptosis via SHP-1-mediated suppression of BCR-ABL and STAT3 signalling in chronic myelogenous leukaemia.. Br J Pharmacol 2015 Jul;172(14):3565-78.
- Bocaneti F, Altamura G, Corteggio A, Velescu E, Borzacchiello G. Expression of bcl-2 and p53 in bovine cutaneous fibropapillomas.. Infect Agent Cancer 2015;10(1):2.
- 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.
- Altamura G, Strazzullo M, Corteggio A, Francioso R, Roperto F, D'Esposito M, Borzacchiello G. O(6)-methylguanine-DNA methyltransferase in equine sarcoids: molecular and epigenetic analysis.. BMC Vet Res 2012 Nov 10;8:218.
- Yuan ZQ, Nicolson L, Marchetti B, Gault EA, Campo MS, Nasir L. Transcriptional changes induced by bovine papillomavirus type 1 in equine fibroblasts.. J Virol 2008 Jul;82(13):6481-91.
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