Author
 |
Schultz Cherry, Stacey |
|
Submitted to: Biochemical and Biophysical Research Communications
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/14/2001 Publication Date: 11/14/2001 Citation: N/A Interpretive Summary: Breast cancer continues to be a leading cause of mortality in women. The recent development of estrogen inhibitory compounds like tamoxifen has increased livibility and provided enhanced therapies for breast cancer patients. The development of tramoxifen-resistant cancers is a major problem in the treatment of breast cancer. Evidence suggests that increases sin transforming growth factor-beta (TGF-beta) activity are directly relate to tamoxifen-resistance. These studies examine the mechanism of the increased TGF-beta activity in breast cancer cell treated with tamoxifen. By determining the mechanism, strategies can be developed to alter tamoxifen-resistance. Technical Abstract: We have found that the enhanced activation of latent TGF-beta by human breast carcinoma cell lines either treated with tamoxifen or deprived of estrogen is dependent upon thrombospondin-1 (TSP-1) since activation was blocked by anti-TSP-1 antibodies or by a TSP antagonist peptide. However, TGF-beta formation upon tamoxifen exposure or estrogen withdrawal is associated with decreased levels of soluble TSP-1. A concomitant increases in the expression of the TSP-1 receptors alphaV beta3 and integrin associated protein (IAP) occurs under these conditions, and antibodies to TSP-1 or to these receptors inhibit increased TGF-beat formation. Therefore, increased cell surface associated TSP-1 enhances latent TGF-beta activation. |
