A Novel Strategy to Isolate Invasion-Inducing Proteins from Human Breast Tumors
Abstract
This proposal utilizes a novel screening strategy that can be applied to the identification of genes involved in metastasis and invasion. The basic approach is so make retroviral-based expression libraries from invasive tumor tissues, and then transfer the invasive phenotype to non-invasive breast tumor cells. This report describes a screen of a library derived from the highly invasive MBA-MB-23l breast tumor cell line. Four cDNAs were recovered in this screen that exhibited an invasive phenotype when retested in the non-invasive MCF-V breast cell line. These cDNAs were sequenced in their entirety and were found to encode DAP-l (a known tumor suppressor), LIPE (hormone sensitive lipase), HSPA5 (heat shock protein) and ABLIM (actin binding protein) . The DAP-l cDNA was orientated in the anti-sense, and was by far the most invasive (20-fold increase vs vector) . Since DAP-l had already been attributed tumor suppressor properties in other biological systems, it was selected for further analysis. Anti-sense expression of DAP-l in NIH 3T3 mouse fibroblasts caused transformation, which was associated with specific activation of the small GTPase RhoA. To summarize, we have successfully screened for invasive cDNAs, and are now characterizing these cDNAs to determine the molecular basis of their transforming activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407444
Entities
People
- Ian P. Whitehead