Systems Biology Research Centre - Tumor biology, School of Life Sciences, University of Skövde, Skövde SE-54128, Sweden.
Cancer Cell Int. 2013 May 15;13(1):43. doi: 10.1186/1475-2867-13-43.
Endometrial adenocarcinoma is the most frequently diagnosed cancer of the female genital tract in the western world. Studies of complex diseases can be difficult to perform on human tumor samples due to the high genetic heterogeneity in human. The use of rat models is preferable since rat has similarities in pathogenesis and histopathological properties to that of human.A genomic region including the highly conserved Phf5a gene associated to development of EAC has previously been identified in an association study. PHF5A has been suggested to acts as a transcription factor or cofactor in the up regulation of expression of Gja1 gene in the presence of estrogen. It has earlier been shown that the Phf5a gene is down regulated in rat EAC derived cell lines by means of expression microarrays.We analyzed the expression of Phf5a and Gja1 by qPCR, and potential relations between the two genes in EAC tumors and non-malignant cell lines derived from the BDII rat model. In addition, the expression pattern of these genes was compared in rat and human EAC tumor samples.Changes in expression for Phf5a/PHF5A were found in tumors from both rat and human even though the observed pattern was not completely consistent between the two species. By separating rat EAC cell lines according to the genetic background, a significant lower expression of Phf5a in one of the two cross backgrounds was revealed, but not for the other. In contrast to other studies, Phf5a/PHF5A regulation of Gja1/GJA1 was not revealed in this study.
子宫内膜腺癌是西方世界女性生殖道最常见的癌症。由于人类遗传异质性高，对复杂疾病的研究很难在人类肿瘤样本上进行。由于大鼠在发病机制和组织病理学特性上与人类相似，因此使用大鼠模型更为可取。先前在一项关联研究中已经确定了一个包括与 EAC 发展相关的高度保守的 Phf5a 基因的基因组区域。PHF5A 被认为在雌激素存在的情况下作为转录因子或辅因子，上调 Gja1 基因的表达。早期已经表明，Phf5a 基因通过表达微阵列在大鼠 EAC 衍生的细胞系中下调。我们通过 qPCR 分析了 Phf5a 和 Gja1 的表达，并在 EAC 肿瘤和源自 BDII 大鼠模型的非恶性细胞系中分析了这两个基因之间的潜在关系。此外，还比较了这些基因在大鼠和人类 EAC 肿瘤样本中的表达模式。尽管在两种物种之间观察到的模式不完全一致，但在来自大鼠和人类的肿瘤中都发现了 Phf5a/PHF5A 的表达变化。通过根据遗传背景分离大鼠 EAC 细胞系，揭示了两种交叉背景中的一种背景下 Phf5a 的表达显著降低，但另一种则没有。与其他研究不同，本研究未揭示 Phf5a/PHF5A 对 Gja1/GJA1 的调控。
