The Effects of Recombinant Synucleins and Insulin-like Growth Factor 1 on Cancer Cell Migration

The synuclein family consists of three distinct genes, alpha-synuclein, beta-synuclein, and gamma-synuclein. The alpha-synuclein and beta-synuclein are predominately expressed in brain and especially alpha-synuclein is related with Parkinson's disease, Alzheimer's disease, and dementia with Lewy bodies. The gamma-synuclein was first identified as breast cancer specific gene 1. It is expressed in the peripheral nervous system and also detected in breast and ovarian cancers. The gamma-synuclein is also known to mediate metastasis of breast and ovarian cancer cells. Insulin-like growth factor 1 (IGF-I) is one of the growth factors that plays an important role in cell proliferation and migration in cancer cells, as well as in normal cells. In this study, we investigated the migrations of SKOV-3, MDAMB-231, and HeLa cells by the recombinant synuclein proteins (alpha-, beta-, and gamma-synucleins) and IGF-I and the molecular mechanism. Furthermore, we investigated the membrane ruffle formation of SKOV-3 cells by recombinant synuclein proteins and IGF-I. As a result, synucleins and IGF-I were found to induce cancer cell migrations. Simultaneous synucleins and IGF-I treatment on the cancer cells induced more migrations than the individual synuclein or IGF-I treatments. The synucleins or IGF-I treatments increased the expressions of membrane-type1 matrix metalloproteinase (MT1-MMP) and cluster of differentiation 44 (CD44). Moreover, simultaneous synucleins and IGF-I treatments further increased the expressions of MT1-MMP and CD44. The synucleins and IGF-I promoted the conformational change of actin filaments, and then this led to the membrane ruffle formation.

The gamma-Synuclein Expression in Breast Cancer and its Correlation with the Expression of the HER-2/neu Gene / 한국유방암학회지

PURPOSE: Synuclein has been identified as an important neuroprotein for developing pathologic deposits in Alzheimer's and Parkinson's disease patients. gamma-synuclein is also known as a breast cancer-specific gene 1 thats's not found in normal breast tissues but it has been reported to be overexpressed in breast cancer, ovarian cancer and other tumors. To evaluate the availability of gamma-synuclein expression as a prognostic factor for infiltrative breast cancer, we analyzed its correlation with the clinical parameters and the HER-2/neu gene expression. METHODS: Two hundred fiffty samples of breast cancer tissues embedded in paraffin and that were obtained from the infiltrative breast cancer patients who were operated in our institution from January 1995 to December 2000 were analyzed with employing the tissue microarray technique. The expression of gamma-synuclein was studied with immunohistochemistry and with using gamma-synulcein antibodies. One hundred thirty one cases that showed favorable staining were selected and studied retrospectively. RESULTS: Fiffty five% (71/131) of the patients showed gamma-synuclein overexpression. The histopathological findings that significantly correlated with gamma-synuclein overexpression were the number of metastatic lymph nodes (p<0.01) and the cancer stage (p<0.01). Using the same tissue mircoarray, the HER-2/neu gene expression and gamma-synuclein expression also showed statistically significant correlation (p=0.04). CONCLUSION: gamma-synuclein overexpression showed significant correaltion with lymph node metastasis and cancer stage. It also showed significant relevance with the HER-2/neu gene expression, and that is already known to be a prognostic factor for breast cancer. Therefore gamma-synuclein may be a useful prognostic factor for infiltrative breast cancer and further studies on the its correlation with survival, local recurrence, and distant metastasis should be conducted