The gene expression response of breast cancer to growth regulators: patterns and correlation with tumor expression profiles.
The gene expression response of breast cancer to growth regulators: patterns and correlation with tumor expression profiles.
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发表时间：
2003-11
期刊：
影响因子：
11.2
通讯作者：
H. Cunliffe;M. Ringnér;S. Bilke;R. Walker;Jennifer Cheung;Yidong Chen;P. Meltzer
中科院分区：
文献类型：
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作者：
H. Cunliffe;M. Ringnér;S. Bilke;R. Walker;Jennifer Cheung;Yidong Chen;P. Meltzer
激素和生长因子信号对基因表达的影响对乳腺肿瘤的发生和疾病进展有重要作用;然而，与生长失调相关的信号网络的靶点还不清楚。我们定义了9种生长和分化调节因子在MCF 7、T-47 D和MDA-MB-436乳腺癌细胞系中引起的动态转录效应（17 β-雌二醇，抗雌激素氟维司群和他莫昔芬，抗雌激素R5020，抗雌激素RU 486，全反式视黄酸，表皮生长因子，丝裂原活化蛋白/细胞外信号调节激酶12抑制剂U 0126和佛波酯12-O-十四酰基佛波-13-乙酸酯），并将基因调控模式与已发表的肿瘤表达谱进行比较。对这些药物的反应的复杂模式揭示了它们的作用之间的意外关系，包括类固醇和表皮生长因子调节的基因的深刻重叠，以及氟维司群和全反式维甲酸之间的惊人重叠。雌激素反应基因可分为两大类，其中只有一类与细胞增殖有关。基因本体分析用于突出对不同有丝分裂原的功能上不同的生物学应答。在患者样本中，几组药物反应基因和区分雌激素受体状态或疾病结果的基因之间存在显著相关性。在我们的数据集中，大多数雌激素受体状态判别因子没有反应，因此可能反映了组织发生和疾病进展的潜在差异，而不是生长因子信号传导。这篇文章强调了乳腺癌生长的不同调节因子在基因表达水平上的总体影响，并将培养中乳腺癌细胞的行为与人类乳腺肿瘤的重要临床特性联系起来。
The effects of hormone and growth factor signaling on gene expression contribute significantly to breast tumorigenesis and disease progression; however, the targets of signaling networks associated with deregulated growth are not well understood. We defined the dynamic transcriptional effects elicited in MCF7, T-47D, and MDA-MB-436 breast cancer cell lines by nine regulators of growth and differentiation (17beta-estradiol, antiestrogens fulvestrant and tamoxifen, progestin R5020, antiprogestin RU486, all-trans-retinoic acid, epidermal growth factor, mitogen-activated protein/extracellular signal-regulated kinase 1/2 inhibitor U0126 and phorbol ester 12-O-tetradecanoylphorbol-13-acetate) and compared the patterns of gene regulation to published tumor expression profiles. The complex pattern of response to these agents revealed unexpected relationships between their effects, including a profound overlap in genes regulated by both steroids and epidermal growth factor, and striking overlaps between fulvestrant and all-trans-retinoic acid. Estrogen-responsive genes could be divided into two major clusters, only one of which is associated with cell proliferation. Gene ontology analysis was used to highlight functionally distinct biological responses to different mitogens. Significant correlations were identified between several clusters of drug-responsive genes and genes that discriminate estrogen receptor status or disease outcome in patient samples. The majority of estrogen receptor status discriminators were not responsive in our dataset and are therefore likely to reflect underlying differences in histogenesis and disease progression rather than growth factor signaling. This article highlights the overall impact at the gene expression level of diverse regulators of breast cancer growth and links the behavior of breast cancer cells in culture to important clinical properties of human breast tumors.