Changes in gene expression associated with overexpression of a novel oncogene. Homo sapiens

Oncogenic drivers are still not obvious in a number of human cancers. Identification of oncogenes that contribute to tumorigenic transformation when overexpressed in their wild-type form, either because of gene amplification or due to some other epigenetic changes, is particularly challenging. This study was carried out to understand the gene expression changes associated with overexpression of a novel oncogene, Methyl CpG Binding Protein 2 (MECP2), that we recently uncovered from a genome-scale screen. Overall design: Immortalized but non-transformed derivatives of human mammary epithelial cells (HMECs) carrying catalytic subunit of human telomerase and SV40 large T and small t antigens, were used as recipient cells for these experiments. We compared changes in gene expression among four different experimental groups: (1) recipient cells overexpressing EGFP (negative control); (2) recipient cells overexpressing MECP2 (our oncogene-of-interest); (3) recipient cells overexpressing activated HRASV12 (which is a classical oncogene); (4) recipient cells overexpressing OTX2 (another known oncogene is medulloblastoma). There were biological duplicates of each experimental group (therefore, with 8 samples in total).

多种人类癌症的致癌驱动因子仍未明确。鉴定在野生型状态下，因基因扩增或其他表观遗传改变而过表达时可促进肿瘤发生转化的致癌基因，极具挑战性。本研究旨在解析我们近期通过全基因组筛选发现的新型致癌基因——甲基CpG结合蛋白2（Methyl CpG Binding Protein 2，MECP2）过表达相关的基因表达变化。实验设计概述：本实验以携带人端粒酶催化亚基、SV40大T抗原与小T抗原的永生化未转化人乳腺上皮细胞（human mammary epithelial cells，HMECs）作为受体细胞。我们比较了四组不同实验组的基因表达变化：(1) 过表达EGFP的受体细胞（阴性对照）；(2) 过表达目标致癌基因MECP2的受体细胞；(3) 过表达激活型HRASV12的受体细胞（经典致癌基因）；(4) 过表达OTX2的受体细胞（另一种已知的髓母细胞瘤相关致癌基因）。每组实验设置两个生物学重复，总样本量共计8份。