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4-HPR可调整卵巢细胞的基因表达

4-HPR modulates gene expression in ovarian cells

Brewer M, Kirkpatrick ND, Wharton JT 2009/5/27 10:50:40

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Int J Cancer, 2006,

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Abstract

Ovarian cancer has a high rate of recurrence and subsequent mortality following chemotherapy despite intense efforts to improve treatment outcomes. Recent trials have suggested that retinoids, especially 4-(N-hydroxyphenyl) retinamide (4-HPR), play an important role as a chemopreventive agent and are currently being used in clinical trials for ovarian cancer chemoprevention as well as treatment. This study examines the mechanism of its activity in premalignant and cancer cells. We investigated the modulation of gene expression by 4-HPR in immortalized ovarian surface epithelial (IOSE) cells and ovarian cancer (OVCA433) cells with DNA microarray. Real time RT-PCR and western blotting were used to confirm the microarray results and metabolic changes were examined with optical fluorescence spectroscopy. 4-HPR resulted in an up-regulation of expression of proapoptotic genes and mitochondrial uncoupling protein in OVCA433 cells and modulation of the RXR receptors in IOSE cells, and down-regulation of mutant BRCA genes in both IOSE and OVCA433 cells. 4-HPR had a larger effect on the redox in the 433 cells compared to IOSE. These findings suggest that 4-HPR acts through different mechanisms in premalignant ovarian surface cells and cancer cells, with a preventive effect in premalignant cells and a treatment effect in cancer cells.

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疾病资源中心

高血压	慢性阻塞性肺病
脂肪性肝病	糖尿病
卒中	肺癌
冠心病	子宫内膜异位症
结直肠癌	乳腺癌
心力衰竭	心律失常

病例分析 [栏目介绍]

甲状腺功能亢进合并黄疸

王燕燕王曙

上海交通大学附属瑞金医院内分泌科

患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。

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