Transgelin, a protein associated with lymph node metastasis in breast cancer
| Autoři | |
|---|---|
| Rok publikování | 2012 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Transgelin is a protein associated with smooth muscle cells (SMC), which was found to be one of the earliest markers of their differentiation from undifferentiated mesenchyme. Transgelin is actin binding protein, whose function is likely associated with stabilization of actin filamenta and Ca2+ independent contraction in SMCs. There is increasing number of studies which describe changed expression of transgelin and its sequential homologue transgelin-2 in connection with cancer. Interestingly, transgelin has been described as both tumor suppressor and biomarker of malignant transformation of the cells in different types of cancer. In our work, we originally focused on identification of novel protein targets of lymph node metastasis in breast cancer. Using 2-D gel electrophoresis we identified transgelin as one of the most overexpressed proteins in metastatic tumors compared to non-metastatic ones. Its expression change was also confirmed at mRNA level using quantitative real-time PCR. Also immunohistochemical (IHC) staining of tumor samples confirmed correlation of transgelin expression with lymph node status of analyzed samples. However, IHC revealed that total transgelin levels in tumors are affected by stromal cell levels rather than by tumor cell levels. These findings indicate that transgelin overexpression in metastatic tumors might be rather a consequence of changes in tumor stroma than a feature of tumor cells. There is only little information concerning function of transgelin in tumors in general and in the process of cancer metastasis. To clarify its function in the breast cancer metastasis, we focused on identification of its interaction partners and on its role in migration properties of tumor cells. To study transgelin protein-protein interactions we have used an approach involving combination of pull-down purification and SILAC metabolic labelling. Thus, we have confirmed transgelin’s known interaction with actin and found new potential interaction partners of transgelin. We further studied the effects of transgelin silencing on migration of the cells. Interestingly, we found that transgelin is able both to promote (in BT549 cells) and to inhibit (in PMC42 cells) migration properties of two different breast cancer cell lines. These findings support ambiguous function of transgelin in tumors, which will need further clarification. |
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