Date of Award

5-2010

Degree Type

Thesis

Degree Name

Departmental Honors

Department

Biology

First Advisor

Daryll B. DeWald

Comments

The BRMS1, BReast cancer Metastasis Supressor 1 gene suppresses cancer metastasis of the MDA-MB-435 human breast carcinoma cell line and the KiSS-1 gene suppresses cancer metastasis of the C8161 human melanoma cell line. While both metastasis suppressor genes suppress secondary tumor formation without preventing orthotopic tumorigenicity, their mechanisms of action are still largely unknown. Cell culture and SDS-PAGE zymography were performed to analyze matrix metalloproteinase (MMP) secretion. Zymography gels were then analyzed by densitometry utilizing the Quantity One software package. Results of the data analysis showed the expression of the BRMS1 and KiSS-1 genes correlate with decreases in secretion of specific MMPs from the cells. In MDA-MB-435, expression of the metastasis suppressor gene BRMS1 reduces secretion of MMP-9 and MMP-2. In C8161, the expression of the metastasis suppressor gene KiSS-1 reduces secretion of MMP-9 and MMP-2. The MMPs are believed to play a role in the invasive potential of cells. By utilizing wound healing assays, the invasive potential of the MDA-MB-435 cells were compared to the non-metastatic MDA-MB- 435/BRMS1 cells. Results showed that expression of BRMS1 in MDA-MB-435 human breast carcinoma cells decreased the initial invasiveness of the cells. These data show that BRMS1 and KiSS-1 impact MMP secretion, suggesting this is part of their mechanism of suppression of invasive potential and metastasis.