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Scientific paper - Original scientific paper
Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma
Cancers, 13 (2021), 11; 2530. https://doi.org/10.3390/cancers13112530
Kafka, Anja; Bukovac, Anja; Brglez, Emilija; Jarmek, Ana-Marija; Poljak, Karolina; Brlek, Petar; Žarković, Kamelija; Njirić, Niko; Pećina-Šlaus, Nives

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Kafka, A., Bukovac, A., Brglez, E., Jarmek, A. M., Poljak, K., Brlek, P. ... Pećina Šlaus, N. (2021). Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma. Cancers, 13. (11). doi: 10.3390/cancers13112530

Kafka, Anja, et al. "Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma." Cancers, vol. 13, no. 11, 2021. https://doi.org/10.3390/cancers13112530

Kafka, Anja, Anja Bukovac, Emilija Brglez, Ana Marija Jarmek, Karolina Poljak, Petar Brlek, Kamelija Žarković, Niko Njirić and Nives Pećina Šlaus. "Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma." Cancers 13, no. 11 (2021). https://doi.org/10.3390/cancers13112530

Kafka, A., et al. (2021) 'Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma', Cancers, 13(11). doi: 10.3390/cancers13112530

Kafka A, Bukovac A, Brglez E, Jarmek AM, Poljak K, Brlek P, and sur.. Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma. Cancers [Internet]. 2021 May 21 [cited 2024 April 19];13(11). doi: 10.3390/cancers13112530

A. Kafka, et al., "Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma", Cancers, vol. 13, no. 11, May 2021. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:337868. [Accessed: 19 April 2024]

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Metadata
Title (english)Methylation Patterns of DKK1, DKK3 and GSK3β Are Accompanied with Different Expression Levels in Human Astrocytoma
AuthorAnja Kafka
AuthorAnja Bukovac
AuthorEmilija Brglez
AuthorAna-Marija Jarmek
AuthorKarolina Poljak
AuthorPetar Brlek
AuthorKamelija Žarković
AuthorNiko Njirić
AuthorNives Pećina-Šlaus
Author's institutionUniversity of Zagreb
School of Medicine
(Croatian Institiute for Brain Research)
Author's institutionUniversity of Zagreb
School of Medicine
(Department of Pathology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Neuroscience
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Pathology
Abstract (english)
In the present study, we investigated genetic and epigenetic changes and protein expression levels of negative regulators of Wnt signaling, DKK1, DKK3, and APC as well as glycogen synthase kinase 3 (GSK3β) and β-catenin in 64 human astrocytomas of grades II–IV. Methylation-specific PCR revealed promoter methylation of DKK1, DKK3, and GSK3β in 38%, 43%, and 18% of samples, respectively. Grade IV comprised the lowest number of methylated GSK3β cases and highest of DKK3. Evaluation of the immunostaining using H-score was performed for β-catenin, both total and unphosphorylated (active) forms. Additionally, active (pY216) and inactive (pS9) forms of GSK3β protein were also analyzed. Spearman’s correlation confirmed the prevalence of β-catenin’s active form (rs = 0.634, p < 0.001) in astrocytoma tumor cells. The Wilcoxon test revealed that astrocytoma with higher levels of the active pGSK3β-Y216 form had lower expression levels of its inactive form (p < 0.0001, Z = −5.332). Changes in APC’s exon 11 were observed in 44.44% of samples by PCR/RFLP. Astrocytomas with changes of APC had higher H-score values of total β-catenin compared to the group without genetic changes (t = −2.264, p = 0.038). Furthermore, a positive correlation between samples with methylated DKK3 promoter and the expression of active pGSK3β-Y216 (rs = 0.356, p = 0.011) was established. Our results emphasize the importance of methylation for the regulation of Wnt signaling. Large deletions of the APC gene associated with increased β-catenin levels, together with oncogenic effects of both β-catenin and GSK3β, are clearly involved in astrocytoma evolution. Our findings contribute to a better understanding of the etiology of gliomas. Further studies should elucidate the clinical and therapeutic relevance of the observed molecular alterations.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleCancers
Numberingvol. 13, no. 11, 2530
e-ISSN2072-6694
DOIhttps://doi.org/10.3390/cancers13112530
URN:NBNurn:nbn:hr:105:337868
Publication2021-05-21
Document URLhttps://www.mdpi.com/2072-6694/13/11/2530
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2021-11-08 09:37:01