Overexpression of Myeloid cell leukemia sequence 1 in Human Endometrial Carcinoma and Its Clinical Significance

• Main Authors: Wan Ting Lien, 連婉婷
• Other Authors: K. H. Lin
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/85892962320824434157

碩士 === 長庚大學 === 生物醫學研究所 === 100 === Endometrial cancer (EC) is one of the most common cancer of the female reproductive system in Europe and the United States. The incidence rate of endometrial cancer is in the second place, and the trend of the mortality rate of endometrial cancer is getting increasing in Taiwan, from thirteenth place to tenth place. To decrease the affect of endometrial cancer on human, we identify some novel proteins which were differential expressed in endometrial cancer as biomarkers for early detection, prognosis and effective anticancer therapy to improve the survival rate. Affymetrix oligonucleotide microarray was performed to identify genes aberrantly expressed in endometrial cancer, and the list of genes was intersected with the available Gene Expression Omnibus (GEO) dataset, GSE20854. Myeloid cell leukemia sequence 1（BCL2-related）, one of the candidate genes over-expression in type Ⅰ（1.34 fold） and type Ⅱ（2.10 fold） cancer, and which is decreased via Iressa（EGF antagonist）treatment, was chosen for further study. Mcl-1 is known to regulate cell survival and apoptosis and its functions are regulated by phosphorylation. Over-expression of Mcl-1 is observed in several type of cancer. The over-expression of Mcl-1 in endometrial cancer tissues were determined by using quantitative-reverse transcription-polymerase chain reaction （Q-RT-PCR）, Western blot, and Immunohistochemistry staining（IHC）. Furthermore, the statistic result of IHC showed that Mcl-1 was highly detected in type Ⅱ endometrial cancer and in the aggressive papillary serous cystadenocarcinoma. To further investigate the role of Mcl-1 gene in endometrial tumorigenesis and progression, we established the Mcl-1 over-expression stable clones in Ishikawa cell line and the Mcl-1 knockdown stable clones in ARK2 cell line, and then the functional analysis were performed. We found that the abilities of cell proliferation, colony formation, migration and invasion were increased in the Mcl-1 over-expression stable clones and were decreased in the Mcl-1 knockdown stable clones. Furthermore, re-expression of Mcl-1 in the Mcl-1 knockdown stable clones can restore these repressed abilities In conclusion, our results indicated that Mcl-1 may play an oncogenic role in endometrial cancer by regulation of tumor cell proliferation and migration.