Significance of Transglutaminase Expression in Multi-Drug Resistant Tumor Cells.

摘要

The resistance of cancer cells to multiple chemotherapeutic agents is a major impediment in the successful treatment of breast cancer. Our results demonstrate that development of multidrug resistance in a human breast cancer cell line (MCF-7) is a result of propagation one or more inherently resistant subclones. One distinct feature associated with the development of multidrug resistance phenotype in breast cancer was that these cells expressed inordinately high levels of a protein cross-linking enzyme, tissue transglutaminase (tTGase). tTGase is a multifunctional protein that in addition to catalyzing protein cross-linking reactions, can bind and hydrolyze GTP and serve as an integrin-binding co-receptor for fibronectin; the features that endows tTGase the properties of a signal transduction molecule. We believe that tTGase expression can confer multidrug resistance phenotype to cancer cells by promoting integrin-mediated cell-survival and cell growth signaling pathways.