Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Int J Mol Sci. 2013 Mar 15;14(3):6090-105. doi: 10.3390/ijms14036090.
PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty.
PAX2 是调节胚胎组织发育和细胞分化的九个 PAX 基因之一。然而,PAX2 在卵巢癌中的功能作用尚不清楚。我们筛选了 26 种具有不同组织起源的卵巢癌细胞系,以检测 PAX2 的表达情况。选择 PAX2 高表达的两种卵巢癌细胞系:RMUGL(黏液性)和 TOV21G(透明细胞性)进行进一步研究。通过靶向 PAX2 基因的慢病毒 shRNAs 实现了这些细胞系中 PAX2 表达的敲低。对 PAX2 稳定敲低细胞进行了细胞增殖、迁移、凋亡、蛋白质谱和基因表达谱的特征分析。结果表明,这些稳定敲低 PAX2 的细胞增殖和迁移能力降低。微阵列分析表明,PAX2 敲低细胞中几个参与生长抑制和运动的基因(如 G0S2、GREM1 和 WFDC1)上调。另一方面,在 PAX2 阴性的卵巢细胞系中过表达 PAX2 抑制了它们的细胞增殖。总之,PAX2 可能具有致癌和肿瘤抑制功能,这可能取决于卵巢癌细胞的遗传组成。进一步研究 PAX2 在肿瘤抑制和死亡率方面的作用是必要的。