Mendoza-Rodriguez Mónica, Arreola Hugo, Valdivia Alejandra, Peralta Raúl, Serna Humberto, Villegas Vanessa, Romero Pablo, Alvarado-Hernández Beatriz, Paniagua Lucero, Marrero-Rodríguez Daniel, Meraz Marco A, Salcedo Mauricio
Laboratorio de Oncogenómica, Unidad de Investigación Médica en Enfermedades Oncológicas, UMAE Hospital de Oncología CMN SXXI, IMSS Av. Cuauhtémoc 330, Col. Doctores, México D.F. 06720 ; Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados IPN, México ; Actual address: AV, Centro Interdisciplinario de Ciencias de la Salud, Unidad Milpa Alta, Instituto Politécnico Nacional Méx.
Int J Clin Exp Pathol. 2013 Aug 15;6(9):1817-25. eCollection 2013.
Cervical Cancer (CC) is one of the most important health problems in women. It frequently presents genetic changes at chromosome region 3q21. This region contains the Cellular Retinol Binding Protein 1 gene (CRBP1) which has been implicated as an important element in the development of other types of cancer. The main goal of the present work was to determine the molecular alterations of CRBP1 and its relationship to CC.
To determine the molecular alterations of CRBP1 gene in CC; twenty-six CC and twenty-six healthy cervix samples were evaluated for: 1) Copy number gain by real-time PCR analysis, 2) expression levels by an immunohistochemistry assay on tissue microarray, and 3) the methylation status of the CRBP1 promoter region.
The increase in CRBP1 copy number was observed in 10 out of the 26 CC samples analyzed, while healthy cervices samples showed no changes in the copy number. In addition, there was a lack of expression of the CRBP1 gene in an important number of the CC samples (17/26), and the CRBP1 gene promoter was methylated in 15/26 of the CC samples. Interestingly, there was a significant association between the lack of expression of the CRBP1 gene and its methylation status.
The data indicates that, both activating and inactivating changes in the CRBP1 gene could be significant events in the development and progression of CC, and the lack of expression of the CRBP1 protein could be related with to the development of CC. We believe that there is enough evidence to consider to CRBP1 gene as a tumor suppressor gene for CC.
宫颈癌(CC)是女性最重要的健康问题之一。它在染色体区域3q21经常出现基因变化。该区域包含细胞视黄醇结合蛋白1基因(CRBP1),该基因被认为是其他类型癌症发展中的一个重要因素。本研究的主要目的是确定CRBP1的分子改变及其与宫颈癌的关系。
为了确定宫颈癌中CRBP1基因的分子改变;对26个宫颈癌样本和26个健康宫颈样本进行了以下评估:1)通过实时PCR分析拷贝数增加情况,2)通过组织微阵列免疫组织化学测定表达水平,3)CRBP1启动子区域的甲基化状态。
在分析的26个宫颈癌样本中,有10个观察到CRBP1拷贝数增加,而健康宫颈样本的拷贝数没有变化。此外,在大量宫颈癌样本(17/26)中缺乏CRBP1基因表达,并且在26个宫颈癌样本中有15个样本的CRBP1基因启动子发生甲基化。有趣的是,CRBP1基因表达缺失与其甲基化状态之间存在显著关联。
数据表明,CRBP1基因的激活和失活变化可能是宫颈癌发生和发展中的重要事件,并且CRBP1蛋白表达缺失可能与宫颈癌的发生有关。我们认为有足够的证据将CRBP1基因视为宫颈癌的肿瘤抑制基因。