Bednarz Natalia, Błaut Krzysztof, Sworczak Krzysztof, Oseka Tomasz, Bielawski Krzysztof P
Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
Acta Biochim Pol. 2009;56(1):83-8. Epub 2009 Mar 4.
Hyperparathyroidism (pHPT) is a relatively frequent endocrinopathy, however, the molecular mechanisms of its etiology remain poorly understood. This disorder is mainly associated with benign tumours (adenoma) and hyperplasia of the parathyroid, hence, the focus is directed also to genes that are likely to be involved in carcinogenesis. Among such genes are ErbB/Her family genes already used in diagnosis of other tumours (e.g., breast carcinoma) and reported also to play a role in development of endocrine lesions. So far, ErbB-1/Her-1/EGFR expression has been detected in pHPT-associated adenomas and hyperplasia as opposed to no expression in normal parathyroid tissue. Moreover, losses or gains of the fragments of chromosomes where ErbB/Her genes are located have been reported. In this study, the gene dosage of ErbB/Her family genes were determined for the first time in parathyroid adenomas, hyperplasia and morphologically unchanged tissue in order to establish their putative role in the development of the disease. Genomic DNA was isolated from 33 patients with sporadic hyperparathyroidism and the gene copy numbers were assessed using real-time PCR. The ErbB/Her genes' profile was unaltered in most of the examined samples. Two low-level amplifications of ErbB-1/Her-1/EGFR gene, two deletions of ErbB-2/Her-2, and six deletions of ErbB-4/Her-4 were found. The ErbB-3/Her-3 gene remained unaffected. No correlation with clinical parameters was found for any gene. Both the low number of alterations and a lack of their associations with clinical parameters exclude the prognostic value of the ErbB/Her genes family in parathyroid tumourigenesis. Nevertheless, the ErbB-4/Her-4 deletions seem to be interesting for further investigations, especially in the context of PTH secretion.
甲状旁腺功能亢进症（pHPT）是一种相对常见的内分泌疾病，然而，其病因的分子机制仍知之甚少。这种疾病主要与甲状旁腺的良性肿瘤（腺瘤）和增生有关，因此，研究重点也指向了可能参与致癌过程的基因。这类基因包括已用于其他肿瘤（如乳腺癌）诊断且据报道也在内分泌病变发展中起作用的ErbB/Her家族基因。到目前为止，已在pHPT相关腺瘤和增生中检测到ErbB-1/Her-1/EGFR表达，而正常甲状旁腺组织中未检测到表达。此外，有报道称ErbB/Her基因所在染色体片段存在缺失或增加。在本研究中，首次测定了甲状旁腺腺瘤、增生及形态学无改变组织中ErbB/Her家族基因的基因剂量，以确定它们在疾病发展中的假定作用。从33例散发性甲状旁腺功能亢进症患者中分离出基因组DNA，并使用实时PCR评估基因拷贝数。在大多数检测样本中，ErbB/Her基因谱未改变。发现ErbB-1/Her-1/EGFR基因有两次低水平扩增、ErbB-2/Her-2有两次缺失以及ErbB-4/Her-4有六次缺失。ErbB-3/Her-3基因未受影响。未发现任何基因与临床参数相关。改变数量少且与临床参数缺乏关联均排除了ErbB/Her基因家族在甲状旁腺肿瘤发生中的预后价值。尽管如此，ErbB-4/Her-4缺失似乎值得进一步研究，尤其是在甲状旁腺激素分泌方面。
