Prevention of the Angiogenic Switch in Human Breast Cancer
Abstract
Our overall goal is to determine if human breast cancer can be prevented from becoming angiogenic when it is still at a microscopic size (< ~ 1 mm3). Some of our key research accomplishments this year are: (i) Heat shock protein-27 (HSP-27) was identified as a gene that was upregulated 27-fold in the angiogenic breast cancer cells MDA-MB-436 as compared to the non-angiogenic dormant breast cancer cells. (ii) Increased expression of HSP-27 was validated by Western blot analysis. (iii) Confirmation of decreased expression of the endogenous angiogenesis inhibitors thrombospondin-1 and endostatin in breast cancer cell lines with a BRCA1 mutation (HCC937). (iv) Demonstration by immunofluorescence of decreased thrombospondin-1 and endostatin expression in sections from human breast tumors with BRCA1 mutations as compared to sections from sporadic breast tumors with wild-type BRCA1. (v) Identification of high levels of prosaposin expression by the non-metastatic breast cancer cell line MDA-MB-231 as compared to the highly metastatic derivatives of this breast cancer cell line that metastasize to bone and lung. (vi) Identification of the secreted protein prosaposin as a regulator of thrombospondin-1 expression in stromal cells. Our studies have potential therapeutic implications to target specific genes that regulate the angiogenic switch, tumor mass expansion, and metastatic disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA481388
Entities
People
- Judah Folkman