Muratovska Aleksandra, Zhou Chaoming, He Shuji, Goodyer Paul, Eccles Michael R
Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand.
Oncogene. 2003 Sep 11;22(39):7989-97. doi: 10.1038/sj.onc.1206766.
The paired-box (PAX) genes encode a family of nine well-characterized paired-box transcription factors, with important roles in development and disease. Although PAX genes are primarily expressed in the embryo, constitutive expression promotes tissue hyperplasia. Rare tumor-specific mutations of PAX genes implicate an oncogenic role, and persistent PAX expression characterizes several tumors. Yet, a cancer-wide analysis of PAX gene expression to investigate a general role for PAX genes has not been performed. We analysed the pattern and requirement for PAX gene expression in a panel of common cancer cell lines. Very frequent PAX gene expression was identified in tumor cell lines, including lymphoma, breast, ovarian, lung, and colon cancer. In addition, the PAX2 gene was frequently expressed in a panel of 406 common primary tumor tissues. Apoptosis was rapidly induced in ovarian and bladder cancer cell lines following RNA interference to silence PAX2 expression, despite concomitant TP53 and/or HRAS mutations. These data suggest that PAX genes are frequently expressed in cancer, and that endogenous PAX gene expression is required for the growth and survival of cancer cells.
成对盒（PAX）基因编码一个由9个特征明确的成对盒转录因子组成的家族，在发育和疾病中发挥重要作用。尽管PAX基因主要在胚胎中表达，但组成性表达会促进组织增生。PAX基因罕见的肿瘤特异性突变表明其具有致癌作用，而PAX基因的持续表达是几种肿瘤的特征。然而，尚未对PAX基因表达进行全癌分析以研究PAX基因的普遍作用。我们分析了一组常见癌细胞系中PAX基因表达的模式和需求。在肿瘤细胞系中发现PAX基因表达非常频繁，包括淋巴瘤、乳腺癌、卵巢癌、肺癌和结肠癌。此外，PAX2基因在一组406个常见原发性肿瘤组织中频繁表达。尽管同时存在TP53和/或HRAS突变，但在RNA干扰使PAX2表达沉默后，卵巢癌和膀胱癌细胞系中迅速诱导了凋亡。这些数据表明PAX基因在癌症中频繁表达，并且内源性PAX基因表达是癌细胞生长和存活所必需的。
