Conde Ana R, Martins Ana P, Brito Miguel, Manuel Armandina, Ramos Sância, Malta-Vacas Joana, Renner Marcus, Poustka Annemarie, Mollenhauer Jan, Monteiro Carolino
Faculdade de Farmacia da Universidade de Lisboa, 1649-003 Lisboa, Portugal.
Int J Oncol. 2007 Jun;30(6):1441-6.
Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved in cell differentiation and protection and has been proposed as a candidate tumour suppressor for brain and epithelial cancer. One study reported a loss of DMBT1 expression in 12.5% (5/40) of gastric cancer samples. Here, we examined in more detail DMBT1 protein and mRNA expression in 78 primary gastric tumour samples and corresponding normal gastric mucosa. DMBT1 was expressed in all non-tumour gastric mucosa tissues. Eleven out of 71 (15%) gastric tumours were negative for the DMBT1 protein in immunohistochemical analyses. Lack of DMBT1 expression was significantly more frequently found in well-differentiated gastric tumours (6/18 well-differentiated tumours vs. 5/53 other subtypes; P=0.025). Quantitative RT-PCR revealed a downregulation of the DMBT1 mRNA for 8/21 (38%) cases, while the remaining 13 cases (62%) displayed a substantial upregulation. Our data suggest that a loss of DMBT1 expression may preferentially take place in well-differentiated gastric carcinoma. However, an upregulation of DMBT1 expression is more frequently found across all gastric cancer types.
高分化胃癌被认为是一种独特的实体,它通过与其他类型胃癌不同的特定分子变化而产生。位于10q25.3 - q26.1的恶性脑肿瘤缺失基因1(DMBT1)编码一种可能参与细胞分化和保护的蛋白质,并且已被提议作为脑癌和上皮癌的候选肿瘤抑制因子。一项研究报道,在40份胃癌样本中有12.5%(5/40)的样本DMBT1表达缺失。在此,我们更详细地检测了78份原发性胃肿瘤样本及相应正常胃黏膜中DMBT1蛋白和mRNA的表达。DMBT1在所有非肿瘤性胃黏膜组织中均有表达。在免疫组织化学分析中,71份胃肿瘤中有11份(15%)DMBT1蛋白呈阴性。在高分化胃肿瘤中,DMBT1表达缺失的情况明显更常见(18份高分化肿瘤中有6份,而其他亚型53份中有5份;P = 0.025)。定量逆转录聚合酶链反应显示,21份样本中有8份(38%)DMBT1 mRNA下调,而其余13份样本(62%)则有显著上调。我们的数据表明,DMBT1表达缺失可能在高分化胃癌中更易发生。然而,在所有类型的胃癌中,DMBT1表达上调更为常见。