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Properties of cellular and serum forms of thymidine kinase 1 (TK1) in dogs with acute lymphocytic leukemia (ALL) and canine mammary tumors (CMTs)

implications for TK1 as a proliferation biomarker

Jagarlamudi, Kiran Kumar and Westberg, Sara and Rönnberg, Henrik and Eriksson, Staffan (2014). Properties of cellular and serum forms of thymidine kinase 1 (TK1) in dogs with acute lymphocytic leukemia (ALL) and canine mammary tumors (CMTs). BMC Veterinary Research. 10:228, 12
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Abstract

Background: Thymidine kinase 1 (TK1) is a eoxyribonucleic acid (DNA) precursor enzyme and a proliferation biomarker used for prognosis and treatment monitoring of breast cancer in humans. The aim was to determine if serum thymidine kinase 1 (sTK1) activity and sTK1 protein levels in dogs with mammary tumors could be useful in
veterinary medicine. Results: Serum samples from 20 healthy dogs and 27 dogs with mammary tumors were analyzed for sTK1 activity,using an [3H]-deoxythymidine (dThd) phosphorylation assay, and for sTK1 protein levels by immune affinity/Western blot assay. The molecular forms of sTK1 in acute lymphocytic leukemia (ALL), canine mammary tumor (CMT), and healthy sera were determined by size exclusion chromatography. Mean sTK1 activities in CMT were 1.0 ± 0.36 pmol/min/mL, differing significantly from healthy dogs (mean ± SD = 0.73 ± 0.26 pmol/min/mL). Serum TK1 protein (26 kDa polypeptide) levels were also significantly higher in CMTs compared to healthy dogs (mean ± SD = 28.5 ± 11.4, and 8.5 ± 4 ng/mL, respectively). Cellular TK1 isolated from ALL tumor cells was predominantly a dimer, while the serum TK1 activity eluted as a high molecular weight (MW) oligomer. In analyses of CMT tissue extracts, TK1 activity eluted in two peaks, a minor peak with a high MW oligomer and a major tetramer peak. Western blot analysis of chromatographic fractions showed that cellular TK1 protein in both ALL and CMT dogs, and to some extent serum TK1 from ALL dogs, correlated with activity profiles, but a large fraction of inactive TK1 protein was detected in CMT. Conclusions: Serum TK1 protein and activity levels were significantly higher in CMT than in healthy dogs. Size exclusion chromatography demonstrated major differences in the molecular forms of sTK1 in ALL, healthy, and CMT dogs, with a large fraction of inactive TK1 protein in CMT. Our results showed that the sTK1 protein assay can differentiate benign tumors (early stage tumors) from healthy more efficiently than sTK1 activity assay. This preliminary data supports that sTK1 protein assay is clinically useful. Further studies are needed to evaluate the diagnostic or prognostic role of serum TK1 protein in CMTs.

Authors/Creators:Jagarlamudi, Kiran Kumar and Westberg, Sara and Rönnberg, Henrik and Eriksson, Staffan
Title:Properties of cellular and serum forms of thymidine kinase 1 (TK1) in dogs with acute lymphocytic leukemia (ALL) and canine mammary tumors (CMTs)
Subtitle:implications for TK1 as a proliferation biomarker
Series/Journal:BMC Veterinary Research (1746-6148)
Year of publishing :2014
Depositing date:2015
Volume:10
Number:228
Page range:12
Number of Pages:12
Publisher:BioMed Central
ISSN:1746-6148
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Full Text Status:Public
Agris subject categories.:L Animal production > L70 Veterinary science and hygiene - General aspects
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Medical Bioscience
Agrovoc terms:veterinary sciences, antibodies, chromatography, dogs
Keywords:canine serum thymidine kinase 1, sTK1 protein assays, canine mammary tumors, size exclusion chromatography, anti-dog TK1 antibodies
URN:NBN:urn:nbn:se:slu:epsilon-e-2497
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-2497
Additional ID:
Type of IDID
Web of Science (WoS)000346805200001
DOI10.1186/s12917-014-0228-1
ID Code:11983
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
(VH) > Dept. of Anatomy, Physiology and Biochemistry
University Animal Hospital (UAH)
Deposited By: SLUpub Connector
Deposited On:16 Mar 2015 15:01
Metadata Last Modified:12 Apr 2015 07:37

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