Human Breast Cancer and Alterations in Methylthioadenosine Phosphorylase
Abstract
Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the conversion of methylthloadenosine (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 and the phenomena of methionine dependent growth, defined as the inability to grow on media containing methionine's metabolic precursor homocysteine. 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. We have created two isogenic breast cancer derived cell lines, one that is MTAP+ and the other that is MTAP-. The MTAP expressing line can 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. Our MTAP deleted cells have increased sensitivity to growth in low levels of methionine and are more sensitive to drugs that inhibit purine biosynthesis. These results suggest that these treatments may be useful in treating MTAP deficient cancers in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA405174
Entities
People
- Warren D Kruger
Organizations
- Fox Chase Cancer Center