Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary.
Int J Mol Sci. 2024 Aug 14;25(16):8831. doi: 10.3390/ijms25168831.
Hematological and oncological diseases are still among the leading causes of childhood mortality. Expression of growth hormone-releasing hormone (GHRH) and its receptors (GHRH-R) has been previously demonstrated in various human tumors, but very limited findings are available about the presence and potential function of GHRH-Rs in oncological and hematological disorders of children. In this study, we aimed to investigate the expression of mRNA for GHRH and splice variant 1 (SV) of GHRH-R in 15 pediatric hematological/oncological specimens by RT-PCR. The presence and binding characteristics of GHRH-R protein were also studied by Western blot and ligand competition assays. Of the fifteen specimens studied, eleven pediatric samples (73%) showed the expression of mRNA for GHRH. These eleven samples also expressed mRNA for GHRH receptor SV1. GHRH-R protein was found to be expressed in two benign tumor samples and five malignant tumors examined by Western blot. The presence of specific, high affinity binding sites on GHRH-R was demonstrated in all of the seven human pediatric solid tumor samples investigated. Our results show that the expression of GHRH and SV1 of GHRH-R in hemato-oncological diseases in children can pave the way for further investigation of GHRH-Rs as potential molecular targets for diagnosis and therapy.
血液学和肿瘤学疾病仍然是儿童死亡的主要原因之一。生长激素释放激素 (GHRH) 及其受体 (GHRH-R) 的表达已在各种人类肿瘤中得到证实,但关于 GHRH-R 在儿童肿瘤和血液系统疾病中的存在和潜在功能的研究结果非常有限。在这项研究中,我们旨在通过 RT-PCR 研究 15 份儿科血液学/肿瘤学标本中 GHRH 和 GHRH-R 剪接变异体 1 (SV) 的 mRNA 表达。还通过 Western blot 和配体竞争测定研究了 GHRH-R 蛋白的存在和结合特性。在研究的十五个标本中,十一个儿科样本(73%)显示出 GHRH 的 mRNA 表达。这十一个样本也表达了 GHRH 受体 SV1 的 mRNA。通过 Western blot 发现 GHRH-R 蛋白在两个良性肿瘤样本和五个恶性肿瘤中表达。在所有研究的七个人类儿科实体瘤样本中均证明了 GHRH-R 上存在特异性、高亲和力结合位点。我们的研究结果表明,儿童血液肿瘤疾病中 GHRH 和 GHRH-R SV1 的表达为进一步研究 GHRH-R 作为潜在的诊断和治疗分子靶点铺平了道路。