Selected ALKBH dioxygenases are overexpressed in salivary gland tumours

Michał Marcinkowski; Damian Garbicz; Tomaš Pilžys; Wojciech Kukwa; Elżbieta Grzesiuk

doi:10.18388/abp.2020_6486

Michał Marcinkowski 1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland; 2Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland
Damian Garbicz 1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland;2Maria Sklodowska-Curie National Research, Institute of Oncology, Warsaw, Poland
Tomaš Pilžys Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
Wojciech Kukwa Department of Otolaryngology, Medical University of Warsaw, Warsaw, Poland
Elżbieta Grzesiuk Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland

DOI: https://doi.org/10.18388/abp.2020_6486

Abstract

Salivary gland tumours (SGTs) are a heterogeneous group of benign tumours of various origins and pathologies, showing a number of DNA modifications. Previously, in malignant head and neck cancer (HNSCC), we found overexpression of ALKBH proteins, the homologs of Escherichia coli AlkB 2-oxoglutarate and Fe(II) dependent dioxygenase. Moreover, we proved the connection of some of these dioxygenases with cancer development. Here, we studied the expression of five of these ALKBH dioxygenases: 1, 3, 4, 5, and FTO in benign SGTs. Using Western blot analysis, we found overexpression of three proteins: ALKBH1, 4, and FTO in SGT as compared to the surrounding, unaffected tissue. ALKBH4 was overexpressed in 76% of patient samples, whereas ALKBH1 and FTO in 65% of the samples. These results differ from those obtained in HNSCC, where FTO overexpression has been observed in 90% of patient samples. We also investigated the relationships between ALKBHs’ expression levels in normal and SGT tissues and identified two correlated pairs: ALKBH1-ALKBH3 and ALKBH1-ALKBH5. Additionally, in tumour tissue ALKBHs: ALKBH1, ALKBH3, ALKBH4, and ALKBH5 levels were correlated with each other. Together, these findings show that the ALKBH proteins exhibit pro cancerogenic action in SGT, even though the levels ALKBHs are generally lower in benign SGT than in malignant HNSCC. We suggest that the overexpression of the ALKBHs, especially FTO, may be used as a cancer marker and for its grading.