Hernández S, Bessa X, Beà S, Hernández L, Nadal A, Mallofré C, Muntane J, Castells A, Fernández P L, Cardesa A, Campo E
Laboratory of Pathology, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Lab Invest. 2001 Apr;81(4):465-73. doi: 10.1038/labinvest.3780254.
cdc25 is a family of cell-cycle phosphatases that activate the cyclin-dependent kinases. cdc25A and B, but not C, have oncogenic potential in vitro. In this study, we analyzed the possible implication of cdc25 genes in the progression of colorectal tumors. RNA and DNA were extracted from 34 paired tumor and normal colorectal tissues and examined by Northern blot, RT-PCR, and Southern blot, respectively. Protein expression was analyzed by Western blot in a subset of normal and tumor samples. The expression levels were correlated with the clinicopathologic characteristics and survival of the patients. cdc25B mRNA was overexpressed in 19 carcinomas (56%). A significant correlation was observed between high cdc25B mRNA levels and the relapse-free, overall, and cancer-related survival of the patients. The cdc25B2 splicing variant was detected in 27 carcinomas (79%) but only in 9 normal samples (26%) and was associated with the grade of the differentiation of the tumors. cdc25A mRNA was overexpressed in four tumors (12%) and cdc25C1 mRNA was overexpressed in nine tumors (26%). A new cdc25C2 splicing variant lacking exon 4 and 5 was identified in all of the tumors and in 56% of the normal samples. No amplifications or gene rearrangements of these genes were detected. In conclusion, these findings indicate that cdc25 isoforms and splicing variants are differentially regulated in colorectal carcinomas and may participate in the development of these tumors. Additionally, the correlation between cdc25B mRNA levels and the survival of the patients also suggest that the cdc25B isoform may be involved in the progression of the disease.
细胞周期蛋白依赖性激酶25（cdc25）是一类激活细胞周期蛋白依赖性激酶的细胞周期磷酸酶。cdc25A和B，而非C，在体外具有致癌潜力。在本研究中，我们分析了cdc25基因在结直肠癌进展中的可能作用。从34对配对的肿瘤和正常结直肠组织中提取RNA和DNA，分别通过Northern印迹、逆转录-聚合酶链反应（RT-PCR）和Southern印迹进行检测。在一部分正常和肿瘤样本中通过蛋白质印迹分析蛋白质表达。将表达水平与患者的临床病理特征和生存率相关联。cdc25B mRNA在19例癌组织中过度表达（56%）。观察到cdc25B mRNA高水平与患者的无复发生存率、总生存率及癌症相关生存率之间存在显著相关性。在27例癌组织中检测到cdc25B2剪接变体（79%），但仅在9例正常样本中检测到（26%），且其与肿瘤的分化程度相关。cdc25A mRNA在4例肿瘤中过度表达（12%），cdc25C1 mRNA在9例肿瘤中过度表达（26%）。在所有肿瘤及56%的正常样本中鉴定出一种缺失外显子4和5的新的cdc25C2剪接变体。未检测到这些基因的扩增或基因重排。总之，这些发现表明，cdc25同工型和剪接变体在结直肠癌中受到不同调控，可能参与这些肿瘤的发生发展。此外，cdc25B mRNA水平与患者生存率之间的相关性还提示cdc25B同工型可能参与疾病进展。
