The role of tetranectin in human breast MCF-7cancer cell line

• Main Authors: Yu-Hsin Chien, 簡幼欣
• Other Authors: Shih-Torng Ding
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/76625480744898399135

碩士 === 國立臺灣大學 === 動物科學技術學研究所 === 100 === Breast cancer is the most common type of cancer in the females worldwide. In recent years, early onset of menarche leads to an increase in the incidence of such cancer in younger woman populations of the world, including Taiwan. Therefore, breast cancer has become a serious health issue for women. Tetranectin (TN) has been found to be a reliable biomarker in certain human carcinoma, including breast cancer, ovary cancer, oral cancer and bladder cancer. Consistently, TN is related to the disease-free and overall survival of breast cancer. Low TN concentrations in human plasma were reported as a high-risk factor for breast cancer metastasis. Interestingly, there has also been shown a strong immunoreactivity in the extracellular matrix associated with breast tumor malignancy. Thus, the purpose of this study was to elucidate the cellular functions of TN and the underlying mechanisms in breast cancer cell line. First, we compared the protein expression of TN in non-tumorigenic epithelial cell line MCF10A, three breast adenocarcinoma cell lines (MCF7, MDA-MB-231 and SKBR3), and the breast ductal carcinoma cell line BT474, and found that TN was detected in both the whole-cell lysates and conditioned media of all breast cancer cell lines, except MCF10A. We then generated the expression constructs of Myc-His-tagged or GFP-fused full-length and signal peptide-deficient TN and transfected each into MCF7 cells to analyze TN-modulated cellular functions. Our results indicate that TN overexpression increased anchorage independent growth in a soft agar assay without affecting cell viability. Interestingly, we also found that TN prominently promoted cell motility, which was not seen for the signal peptide-deficient TN, indicating a role of TN in modulating cell movement is be an extracellular stimulator. In conclusion, we demonstrated in this study that TN is normally up-regulated in breast cancer cell lines, but not in normal breast epithelial cells. When overexpressed, TN increases cell motility and anchorage independent growth in MCF7cell, without affecting cell survival. These support the hypothesis that TN plays an important role in tumor development of breast cancer. Nevertheless, the molecular mechanisms underlying TN-mediated tumor progression remain to be elucidated.