Genetic Determinants of Breast Cancer Metastasis
Abstract
Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the pathway which converts methylthioadenosine (MTA) into methionine and adenine. The MTAP gene is frequently deleted in a variety of different cancers. Our lab has found a link between loss of MTAP expression and the phenomena of methionine dependent growth, defined as the inability to grow on media containing methionine's metabolic precursor homocysteine. Thus, cells lacking MTAP seem to require excess methionine for growth. Other labs have shown that cells lacking MTAP have increased sensitivity to purine biosynthetic inhibitors such as methotrexate and 5, 10-dideazatetrahydrofolate. These observations suggest that an effective two-pronged strategy could be used to eliminate MTAP negative breast cancer cells in vivo. Over the past year we have created isogenic breast cancer derived cell lines, one that is deleted for MTAP and one that has had it reintroduced. We have discovered that the cell line with MTAP reintroduced can now use MTA to make methionine, but is still unable to grow on media lacking homocysteine. This result suggests that MTAP deletion is not the primary cause of methionine dependent growth. These cell lines will be vital tools in our experiments over the next twelve months.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA387704
Entities
People
- Warren D Kruger
Organizations
- Fox Chase Cancer Center