在雌激素受體不表達乳癌中辨別ENSA為候選目標

Identification of ENSA as a Candidate Target in Estrogen Receptor Non-expressing Breast Cancer

邱子容(ZI-JUNG CHIU)

指導教授 ： 呂昱瑋

國立中正大學/理學院/生命科學系分子生物研究所/碩士(2016年)

摘要

在過去的研究中假設抑癌基因 (Tumor suppressor genes) 或二維基因座 (Bivalent loci)異常的去氧核醣核酸甲基化 (DNA methylation) 會導致癌症，因此我的研究主要是: 辨認關鍵的抑癌基因或二維基因座的甲基化是否對於乳癌的發生是必須的。從79對乳癌病人檢體中，我們發現在乳癌病人檢體中的腫瘤區域和相鄰的正常區域中，抑癌基因RassF1A異常甲基化情形有顯著差異。另外，二維基因座ENSA的甲基化也在早期與晚期的乳癌中有顯著差異。接著將表達RassF1A及HIC1之質體轉染至MDA-MB-231及MCF7細胞中，以聚合酶連鎖反應及西方點墨法驗證，並以免疫染色螢光觀察過度表達之細胞，另外透過MTT assay發現在MDA-MB-231細胞中RassF1A及HIC1過度表達會使細胞生長速率下降，在MCF7細胞中則無此情形。

關鍵字

對位性基因體學 ； 去氧核醣核酸甲基化 ； 乳癌

並列摘要

Abnormal DNA methylation within tumor suppressor (TS) genes and/or bivalent loci was hypothesized to cause cancer. Therefore, we aimed to identify the crucial TS or bivalent loci that their methylation might be sufficient for the development of breast cancer. From 79 pairs of breast cancer samples, we found significant RassF1A methylation differences between the tumor and adjacent normal parts. On the other hand, the abnormal ENSA methylation was found to correlate with low and high stage breast cancer progression. At last, overexpressed RassF1A and HIC1 in breast cancer cell lines, MDA-MB-231 and MCF7, was validated by immunostaining and found to only reduce the cell proliferation rate in MDA-MB-231.

並列關鍵字

Epigenetics ； DNA methylation ； Breast cancer

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