Introduction: The molecular mechanism of metastatic bone disease in breast cancer remains unknown. Bone marrow stromal cell antigen 2 (BST2) was previously described in melanoma. We recently made the novel observation of BST2 protein expression in human breast cancer cell lines. The purpose of our present study was to investigate the expression of BST2 in primary breast cancer and its association with the development of metastatic breast cancer to bone. Materials and Methods:. cDNA microarray analysis was used to compare BST2 gene expression in a primary human breast cancer cell line (MDA-231) and a metastatic to bone (MTB) human breast cancer cell line (MDA-231 BO). BST2 expression in 8 MTB breast cancer cell lines and 4 primary breast cancer cell lines was also compared using real-time RT-PCR and Western blot assay. We employed tissue array to study BST2 expression in human breast cancer using array slides containing: 30 independent MTB primary breast cancers, 20 non-metastasis forming breast cancers and 4 normal breast tissues. The relationship between BST2 expression, cell growth and apoptosis was studied in a human breast recombinant model system using FACS analysis. Results: Microarray demonstrated over expression of the BST2 gene in the MTB breast cancer cell line MDA-231 BO compared to the primary human breast cancer cell line MDA-231. BST2 was expressed in 80% (7 of 8) of MTB breast cancer cell lines and 0% (0 of 4) non-metastatic breast cancer cell lines as measured by real-time RT-PCR and Western blot assay. Tissue array BST2 expression was observed in over 70% of the cells in each of the 30 MTB bone breast cancer primaries studied. In contrast BST2 expression was observed in 30 to 70% of cells in each of the 20 non-metastatic breast cancer primaries studied (P<.001). Breast cell lines transfected with BST2 demonstrated increased BST2 expression which was associated with increased S phase of the cell cycle as measured by FACS. Conclusion: These results provide novel data indicating BST2 gene and protein expression is associated with the formation of bone metastases in human breast cancer.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]