Marcinkowski Michał, Garbicz Damian, Pilžys Tomaš, Kukwa Wojciech, Grzesiuk Elżbieta
1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland; 2Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland;2Maria Sklodowska-Curie National Research, Institute of Oncology, Warsaw, Poland.
Acta Biochim Pol. 2022 Dec 2;69(4):889-894. doi: 10.18388/abp.2020_6486.
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.
唾液腺肿瘤(SGTs)是一组起源和病理各异的异质性良性肿瘤,表现出多种DNA修饰。此前,在恶性头颈部癌(HNSCC)中,我们发现了ALKBH蛋白的过表达,这些蛋白是大肠杆菌AlkB 2-氧代戊二酸和铁(II)依赖性双加氧酶的同源物。此外,我们证明了其中一些双加氧酶与癌症发展的关联。在此,我们研究了这五种ALKBH双加氧酶:1、3、4、5和FTO在良性SGTs中的表达。通过蛋白质免疫印迹分析,我们发现与周围未受影响的组织相比,SGT中三种蛋白:ALKBH1、4和FTO过表达。76%的患者样本中ALKBH4过表达,而65%的样本中ALKBH1和FTO过表达。这些结果与在HNSCC中获得的结果不同,在HNSCC中90%的患者样本中观察到FTO过表达。我们还研究了正常组织和SGT组织中ALKBHs表达水平之间的关系,确定了两对相关组合:ALKBH1-ALKBH3和ALKBH1-ALKBH5。此外,在肿瘤组织中,ALKBHs:ALKBH1、ALKBH3、ALKBH4和ALKBH5的水平相互关联。总之,这些发现表明,ALKBH蛋白在SGT中表现出促癌作用,尽管良性SGT中ALKBHs的水平通常低于恶性HNSCC。我们建议,ALKBHs的过表达,尤其是FTO,可作为癌症标志物及其分级的依据。